人铜转运蛋白1胞外蛋氨酸富集区与银离子相互作用的研究
摘要
人类铜离子传输体蛋白1（hCtr1）是一种糖基化的膜蛋白，同时也是高度保守的铜离子传输体蛋白家族中的一员。它由190个氨基酸残基组成，包含三个假定的跨膜区域、一个胞外的N端区域和一个胞内的C端区域。胞外N端区域有两个蛋氨酸残基富集的区域和两个组氨酸残基富集的区域，它们对于hCtr1蛋白传输铜离子和银离子起重要作用。
在本论文中，我们运用圆二色谱法（CD）、核磁共振波谱法（NMR）以及等温滴定微量热法（ITC）等实验方法研究了包含hCtr1蛋白N端蛋氨酸富集区M2在内的一个20肽及其突变体在SDS胶束溶液中与Ag(I)的配位方式以及配位过程中的热力学性质。CD实验表明原始肽WT在SDS胶束溶液中形成了部分螺旋结构。NMR实验结果进一步表明肽在SDS胶束中形成了C端为螺旋、N端为灵活区域的结构。顺磁性探针实验表明，Gly1-Pro11区域内的氨基酸残基位于胶束的表面，而Met12-Asn20氨基酸残基则插入到胶束内部。在加入Ag(I)后，CD和NMR实验结果都表明肽与Ag(I)发生了相互作用。肽段中所有Met的δ_(H_γ)和δ_(H_ε)均向低场方向移动，这说明Met与Ag(I)结合。结合2D-NOESY谱和2D-TOCSY谱我们发现第7位、第8位和第12位的Met提供了强的配位，第9位的Met提供了弱的配位，而第10位的Met不参与配位。
为进一步研究WT与Ag(I)的相互作用，我们进行了ITC实验。通过ITC实验我们得到了WT及各种突变体肽与Ag(I)在SDS胶束溶液中的相互作用的热力学参数，如结合常数K、结合位点数n、结合反应焓变ΔH、熵变ΔS以及吉布斯自由能G。通过分析得到的热力学参数，我们发现WT在SDS胶束中与Ag(I)以1:1的方式结合，结合常数为1.12×10~5M~(-1)，亲和力比较弱，结合过程为焓驱动过程。与WT在SDS胶束溶液中与Ag(I)的配位结果相比，M7A、M8A和M12A的热力学参数（主要是熵变和结合位点数）完全不同，M9A的热力学参数则发生很大变化。ITC实验结果进一步证明了NMR的结果，即残基Met7、Met8、Met12（hCtr1中第40、41和45位蛋氨酸）在hCtr1-M2与Ag(I)的结合中起非常重要的作用，Met9（hCtr1中第42位蛋氨酸）的配位强度比它们弱些，而Met10（hCtr1中第43位蛋氨酸）则不参与配位。
我们希望这些研究发现能为揭示铜转运蛋白传输Ag(I)的机制提供一些有用的信息。
Human copper transporter1(hCtr1) is a glycosylated membrane protein and amember of a highly conserved copper transporter family. The hCtr1is composed of190amino acids, including three putative transmembrane domains, an extracellularN-terminal region and an intracellular C-terminal region. A recent structural study bycryoelectron crystallography revealed that hCtr1forms a symmetrical homotrimerwith a channel-like architecture in order to allow import of Cu(I). The extracellularN terminus of hCtr1contains two methionine (Met)-rich and two histidine (His)-richmotifs that are thought to be essential for the function of the transporter. Althoughconsiderable progress has been made toward understanding the structure-functionaspects of hCtr1-mediated Cu transport, details on the interaction of hCtr1proteinwith Ag at an atomic level is still poorly understood.
In this work, we studied the coordination and thermodynamic characteristics ofAg(I) binding with a20-residue peptide including hCtr1-M2region and its mutantswith Met/Ala substitution in SDS micellar solution using CD, NMR and ITCmethods. The CD experiment shows that the WT peptide forms an-helix structurein SDS micelles. The2D-NMR experiments show that the peptide forms an-helixstructure in the C-terminal region and the N-terminal region is flexible in SDSmicelles. The paramagnetic probe experiment suggests that the residues from Gly1to Pro11are exposed to water and the residues from Met12to Asn20embedded inthe micelles. Both CD and NMR experiments indicate that the secondary structure ofWT changed upon adding the Ag(I). In the NMR spectra of the peptide, we observethe downfield shifting of the peaks associated with the γ and ε protons of methionineresidues upon the addition of Ag(I), suggesting that the thioethers of methioninesparticipate in coordination with Ag(I). The residues of methionines at position7,8,9 and12of the N-terminal region provide a strong coordination in the binding withsilver, while the residue Met10is not involved in the coordination.
We also perform the ITC experiments to further study of the interactionsbetween Ag(I) and the hCtr1-M2peptide. We obtain the thermodynamic parametersof the binding of WT and various mutant peptides with Ag(I) in SDS micellarsolution, such as the binding constant K, the number of binding sites n, enthalpychange H, entropy change S and Gibbs free energy change G. Through analysisof the thermodynamic data, we found that the WT peptide binds Ag(I) at1:1ratiowith a relative weak affinity (K=1.12×10~5M~(-1)), driven by enthalpy change.Compared with the results of coordination of WT with Ag(I) in SDS micelles, thethermodynamic data of the mutants M7A, M8A and M12A are dramatically different(particularly in n and S) and those of M9A are largely different. The results of ITCfurther prove the results of the NMR, namely, the residue Met7, Met8and Met12(the methionine residues at the position40,41and45in hCtr1protein) play animportant role in the coordination of the hCtr1-M2peptide with silver, Met9(themethionine residue at the position42in hCtr1protein）also play a role in the bindingwith a relative weaker affinity, while Met10(Met43in hCtr1protein) is not involvedin the coordination.
We hope that these findings will provide some insight into the mechanism ofhCtr1transporting Ag(I).
在本论文中，我们运用圆二色谱法（CD）、核磁共振波谱法（NMR）以及等温滴定微量热法（ITC）等实验方法研究了包含hCtr1蛋白N端蛋氨酸富集区M2在内的一个20肽及其突变体在SDS胶束溶液中与Ag(I)的配位方式以及配位过程中的热力学性质。CD实验表明原始肽WT在SDS胶束溶液中形成了部分螺旋结构。NMR实验结果进一步表明肽在SDS胶束中形成了C端为螺旋、N端为灵活区域的结构。顺磁性探针实验表明，Gly1-Pro11区域内的氨基酸残基位于胶束的表面，而Met12-Asn20氨基酸残基则插入到胶束内部。在加入Ag(I)后，CD和NMR实验结果都表明肽与Ag(I)发生了相互作用。肽段中所有Met的δ_(H_γ)和δ_(H_ε)均向低场方向移动，这说明Met与Ag(I)结合。结合2D-NOESY谱和2D-TOCSY谱我们发现第7位、第8位和第12位的Met提供了强的配位，第9位的Met提供了弱的配位，而第10位的Met不参与配位。
为进一步研究WT与Ag(I)的相互作用，我们进行了ITC实验。通过ITC实验我们得到了WT及各种突变体肽与Ag(I)在SDS胶束溶液中的相互作用的热力学参数，如结合常数K、结合位点数n、结合反应焓变ΔH、熵变ΔS以及吉布斯自由能G。通过分析得到的热力学参数，我们发现WT在SDS胶束中与Ag(I)以1:1的方式结合，结合常数为1.12×10~5M~(-1)，亲和力比较弱，结合过程为焓驱动过程。与WT在SDS胶束溶液中与Ag(I)的配位结果相比，M7A、M8A和M12A的热力学参数（主要是熵变和结合位点数）完全不同，M9A的热力学参数则发生很大变化。ITC实验结果进一步证明了NMR的结果，即残基Met7、Met8、Met12（hCtr1中第40、41和45位蛋氨酸）在hCtr1-M2与Ag(I)的结合中起非常重要的作用，Met9（hCtr1中第42位蛋氨酸）的配位强度比它们弱些，而Met10（hCtr1中第43位蛋氨酸）则不参与配位。
我们希望这些研究发现能为揭示铜转运蛋白传输Ag(I)的机制提供一些有用的信息。
Human copper transporter1(hCtr1) is a glycosylated membrane protein and amember of a highly conserved copper transporter family. The hCtr1is composed of190amino acids, including three putative transmembrane domains, an extracellularN-terminal region and an intracellular C-terminal region. A recent structural study bycryoelectron crystallography revealed that hCtr1forms a symmetrical homotrimerwith a channel-like architecture in order to allow import of Cu(I). The extracellularN terminus of hCtr1contains two methionine (Met)-rich and two histidine (His)-richmotifs that are thought to be essential for the function of the transporter. Althoughconsiderable progress has been made toward understanding the structure-functionaspects of hCtr1-mediated Cu transport, details on the interaction of hCtr1proteinwith Ag at an atomic level is still poorly understood.
In this work, we studied the coordination and thermodynamic characteristics ofAg(I) binding with a20-residue peptide including hCtr1-M2region and its mutantswith Met/Ala substitution in SDS micellar solution using CD, NMR and ITCmethods. The CD experiment shows that the WT peptide forms an-helix structurein SDS micelles. The2D-NMR experiments show that the peptide forms an-helixstructure in the C-terminal region and the N-terminal region is flexible in SDSmicelles. The paramagnetic probe experiment suggests that the residues from Gly1to Pro11are exposed to water and the residues from Met12to Asn20embedded inthe micelles. Both CD and NMR experiments indicate that the secondary structure ofWT changed upon adding the Ag(I). In the NMR spectra of the peptide, we observethe downfield shifting of the peaks associated with the γ and ε protons of methionineresidues upon the addition of Ag(I), suggesting that the thioethers of methioninesparticipate in coordination with Ag(I). The residues of methionines at position7,8,9 and12of the N-terminal region provide a strong coordination in the binding withsilver, while the residue Met10is not involved in the coordination.
We also perform the ITC experiments to further study of the interactionsbetween Ag(I) and the hCtr1-M2peptide. We obtain the thermodynamic parametersof the binding of WT and various mutant peptides with Ag(I) in SDS micellarsolution, such as the binding constant K, the number of binding sites n, enthalpychange H, entropy change S and Gibbs free energy change G. Through analysisof the thermodynamic data, we found that the WT peptide binds Ag(I) at1:1ratiowith a relative weak affinity (K=1.12×10~5M~(-1)), driven by enthalpy change.Compared with the results of coordination of WT with Ag(I) in SDS micelles, thethermodynamic data of the mutants M7A, M8A and M12A are dramatically different(particularly in n and S) and those of M9A are largely different. The results of ITCfurther prove the results of the NMR, namely, the residue Met7, Met8and Met12(the methionine residues at the position40,41and45in hCtr1protein) play animportant role in the coordination of the hCtr1-M2peptide with silver, Met9(themethionine residue at the position42in hCtr1protein）also play a role in the bindingwith a relative weaker affinity, while Met10(Met43in hCtr1protein) is not involvedin the coordination.
We hope that these findings will provide some insight into the mechanism ofhCtr1transporting Ag(I).
引文
[1] DRAKE P L, HAZELWOOD K J. Exposure-related health effects of silver andsilver compounds: a review [J]. Annals of Occupational Hygiene,2005,49(7):575-585.
[2] MODAK S M, SAMPATH L, FOX JR C. Combined topical use of silversulfadiazine and antibiotics as a possible solution to bacterial resistance in burnwounds [J]. Journal of Burn Care&Research,1988,9(4):359-363.
[3] TROP M, NOVAK M, RODL S, et al. Silver-coated dressing acticoat causedraised liver enzymes and argyria-like symptoms in burn patient [J]. The Journalof trauma,2006,60(3):648-652.
[4]刘康时,江显异,赵英.银系无机抗菌剂作用机理的研究进展[J].佛山陶瓷,2001,11(56):1-5.
[5]陈四红,吕曼祺,张敬党, et al.含Cu抗菌不锈钢的微观组织及其抗菌性能[J].金属学报,2004,40(3):314-318.
[6]墙蔷,倪红卫,幸伟, et al.银的抗菌作用机理[J].武汉科技大学学报:自然科学版,2007,30(2):121-124.
[7] FENG Q, WU J, CHEN G, et al. A mechanistic study of the antibacterial effectof silver ions on Escherichia coli and Staphylococcus aureus [J]. Journal ofbiomedical materials research,2000,52(4):662-668.
[8] LING FENG Q, NAM KIM T, WU J, et al. Antibacterial effects of Ag-HApthin films on alumina substrates [J]. Thin Solid Films,1998,335(1-2):214-219.
[9]康湛莹,李瑞增.重金属离子杀菌作用的机理[J].哈尔滨科学技术大学学报,1995,19(003):103-106.
[10] LIAU S, READ D, PUGH W, et al. Interaction of silver nitrate with readilyidentifiable groups: relationship to the antibacterialaction of silver ions [J].Letters in Applied Microbiology,1997,25(4):279-283.
[11]余海霞,张泽强.戴银型抗菌累托石的制备及其性能[J].武汉化工学院学报,2003,25(1):46-48.
[12] INOUE Y, HOSHINO M, TAKAHASHI H, et al. Bactericidal activity ofAg–zeolite mediated by reactive oxygen species under aerated conditions [J].Journal of inorganic biochemistry,2002,92(1):37-42.
[13] DAVIES R L, ETRIS S F. The development and functions of silver in waterpurification and disease control [J]. Catalysis Today,1997,36(1):107-114.
[14] MIAO A J, SCHWEHR K A, XU C, et al. The algal toxicity of silverengineered nanoparticles and detoxification by exopolymeric substances [J].Environmental Pollution,2009,157(11):3034-3041.
[15] HARTFORD C E, ZIFFREN S E. The use of0.5%silver nitrate in burns:results in220patients [J]. The Journal of trauma,1972,12(8):682-688.
[16] FABREGA J, FAWCETT S R, RENSHAW J C, et al. Silver nanoparticle impacton bacterial growth: Effect of pH, concentration, and organic matter [J].Environmental science&technology,2009,43(19):7285-7290.
[17] BERTINATO J, CHEUNG L, HOQUE R, et al. Ctr1transports silver intomammalian cells [J]. Journal of Trace Elements in Medicine and Biology,2010,24(3):178-184.
[18] GULBRANSON S H, HUD J A, HANSEN R C. Argyria following the use ofdietary supplements containing colloidal silver protein [J]. Cutis,2000,66(5):373-376.
[19] SHELLEY W B, SHELLEY E D, BURMEISTER V. Argyria: The intradermal[J]. Journal of the American Academy of Dermatology,1987,16(1):211-217.
[20] BALDI C, MINOIA C, NUCCI A D, et al. Effects of silver in isolated rathepatocytes [J]. Toxicology letters,1988,41(3):261-268.
[21] SHINOGI M, MAEIZUMI S. Effect of preinduction of metallothionein ontissue distribution of silver and hepatic lipid peroxidation [J]. Biological&pharmaceutical bulletin,1993,16(4):372-374.
[22] HOLLINGER M A. Toxicological aspects of topical silver pharmaceuticals [J].CRC Critical Reviews in Toxicology,1996,26(3):255-260.
[23] GAMELLI R L, PAXTON T P, O'REILLY M. Bone marrow toxicity by silversulfadiazine [J]. Surgery, gynecology&obstetrics,1993,177(2):115-120.
[24] ZAPATA-SIRVENT R L, HANSBROUGH J F. Cytotoxicity to humanleukocytes by topical antimicrobial agents used for burn care [J]. The Journal ofburn care&rehabilitation,1993,14(2Pt1):132-140.
[25] HULTMAN P, ENESTR M S, TURLEY S, et al. Selective induction ofanti‐fibrillarin autoantibodies by silver nitrate in mice [J]. Clinical&Experimental Immunology,1994,96(2):285-291.
[26] STEFFENSEN I, MESNA O, ANDRUCHOW E, et al. Cytotoxicity andaccumulation of Hg, Ag, Cd, Cu, Pb and Zn in human peripheral T and Blymphocytes and monocytes in vitro [J]. General Pharmacology: The VascularSystem,1994,25(8):1621-1633.
[27] JANSSON G, HARMS-RINGDAHL M. Stimulating effects of mercuric-andsilver ions on the superoxide anion production in human polymorphonuclearleukocytes [J]. Free Radical Research,1993,18(2):87-98.
[28] SILVER S. Bacterial silver resistance: molecular biology and uses and misusesof silver compounds [J]. FEMS microbiology reviews,2003,27(2‐3):341-353.
[29] ROPER W. Toxicological profile for silver [J].Agency for Toxic Substances andDisease Registry, US Public Health Service, Atlanta, GA,1990.
[30] WAN A T, CONYERS R, COOMBS C J, et al. Determination of silver in blood,urine, and tissues of volunteers and burn patients [J]. Clinical chemistry,1991,37(10):1683-1687.
[31] CATSAKIS L, SULICA V. Allergy to silver amalgams [J]. Oral Surgery, OralMedicine, Oral Pathology,1978,46(3):371-375.
[32] SATO S, SUEKI H, NISHIJIMA A. Two unusual cases of argyria: theapplication of an improved tissue processing method for X-ray microanalysis ofselenium and sulphur in silver-laden granules [J]. British Journal ofDermatology,1999,140:158-163.
[33] SAINT S, VEENSTRA D L, SULLIVAN S D, et al. The potential clinical andeconomic benefits of silver alloy urinary catheters in preventing urinary tractinfection [J]. Archives of Internal Medicine,2000,160(17):2670-2675.
[34] RONGIOLETTI F, ROBERT E, BUFFA P, et al. Blue nevi-like dottedoccupational argyria [J]. Journal of the American Academy of Dermatology,1992,27(6Pt1):1015-1016.
[35] FURCHNER J, RICHMOND C, DRAKE G. Comparative metabolism ofradionuclides in mammals-IV. Retention of silver-110m in the mouse, rat,monkey, and dog [J]. Health physics,1968,15(6):505-514.
[36] KLEIN D A. Environmental Impacts of Artificial Ice Nucleating Agents.Dowden, Hutchinson&Ross [J]. Inc, Stroudburg, Pennsylvania,1978,169-175.
[37] ROSENMAN K, MOSS A, KON S. Argyria: clinical implications of exposureto silver nitrate and silver oxide [J]. Journal of Occupational and EnvironmentalMedicine,1979,21(6):430-435.
[38] SUE Y M, YU-YUN LEE J, WANG M C, et al. Generalized argyria in twochronic hemodialysis patients [J]. American journal of kidney diseases,2001,37(5):1048-1051.
[39] ROSENMAN K, SEIXAS N, JACOBS I. Potential nephrotoxic effects ofexposure to silver [J]. British journal of industrial medicine,1987,44(4):267-272.
[40] FRANCIS W. Health hazard from occupational exposure to metallic copper andsilver dust [J]. The American Industrial Hygiene Association Journal,1979,40(3):245-247.
[41] VENUGOPAL B, LUCKEY T. Metal toxicity in mammals.[J]. Chemicaltoxicity of metals and metalloids, Acedemic Press,1978,32-36.
[42] SHELLEY W B, SHELLEY E D, BURMEISTER V. Argyria: the intradermal"photograph", a manifestation of passive photosensitivity [J]. Journal of theAmerican Academy of Dermatology,1987,16(1):211-217.
[43] FUNG M C, BOWEN D L. Silver products for medical indications: risk-benefitassessment [J]. Clinical Toxicology,1996,34(1):119-126.
[44] PETRIS M J, MERCER J, CULVENOR J G, et al. Ligand-regulated transportof the Menkes copper P-type ATPase efflux pump from the Golgi apparatus tothe plasma membrane: a novel mechanism of regulated trafficking [J]. TheEMBO journal,1996,15(22):6084-6095.
[45] VERHEIJEN F W, BEERENS C, HAVELAAR A C, et al. Fibroblast silverloading for the diagnosis of Menkes disease [J]. Journal of medical genetics,1998,35(10):849-851.
[46] IBRICEVIC A, BRODY S L, YOUNGS W J, et al. ATP7B detoxifies silver inciliated airway epithelial cells [J]. Toxicology and applied pharmacology,2010,243(3):315-322.
[47] LEE J, PE A M M O, NOSE Y, et al. Biochemical characterization of the humancopper transporter Ctr1[J]. Journal of Biological Chemistry,2002,277(6):4380-4387.
[48] PETRIS M J, SMITH K, LEE J, et al. Copper-stimulated endocytosis anddegradation of the human copper transporter, hCtr1[J]. Journal of BiologicalChemistry,2003,278(11):9639-9646.
[49] KIM H, SON H Y, BAILEY S M, et al. Deletion of hepatic Ctr1reveals itsfunction in copper acquisition and compensatory mechanisms for copperhomeostasis [J]. American Journal of Physiology-Gastrointestinal and LiverPhysiology,2009,296(2): G356-G364.
[50] ZIMNICKA A M, MARYON E B, KAPLAN J H. Human copper transporterhCTR1mediates basolateral uptake of copper into enterocytes [J]. Journal ofBiological Chemistry,2007,282(36):26471-26480.
[51] BERTINATO J, SWIST E, PLOUFFE L, et al. Ctr2is partially localized to theplasma membrane and stimulates copper uptake in COS-7cells [J]. Biochem J,2008,409:731-740.
[52] ABADA P, HOWELL S B. Regulation of Cisplatin Cytotoxicity by Cu InfluxTransporters [J]. Metal-based drugs,2010,317581-317589.
[53] EISSES J F, KAPLAN J H. Molecular characterization of hCTR1, the humancopper uptake protein [J]. Journal of Biological Chemistry,2002,277(32):29162-29171.
[54] GITSCHIER J, MOFFAT B, REILLY D, et al. Solution structure of the fourthmetal-binding domain from the Menkes copper-transporting ATPase [J]. NatureStructural&Molecular Biology,1998,5(1):47-54.
[55] YAMAGUCHI Y, HEINY M, GITLIN J. Isolation and characterization of ahuman liver cDNA as a candidate gene for Wilson disease [J]. Biochemical andbiophysical research communications,1993,197(1):271-277.
[56] SCHAEFER M, HOPKINS R G, FAILLA M L, et al. Hepatocyte-specificlocalization and copper-dependent trafficking of the Wilson’s disease protein inthe liver [J]. American Journal of Physiology-Gastrointestinal and LiverPhysiology,1999,276(3): G639-G646.
[57]张英丽,鹿欣,丰有吉.铜离子转运蛋白家族与卵巢癌顺铂耐药关系的研究进展[J].现代妇产科进展,2007,16(5):388-390.
[58] LEE J, PROHASKA J R, DAGENAIS S L, et al. Isolation of a murine coppertransporter gene, tissue specific expression and functional complementation of ayeast copper transport mutant [J]. Gene,2000,254(1-2):87-96.
[59] PETRIS M J. The SLC31(Ctr) copper transporter family [J]. Pflügers ArchivEuropean Journal of Physiology,2004,447(5):752-755.
[60] DANCIS A, HAILE D, YUAN D S, et al. The Saccharomyces cerevisiaecopper transport protein (Ctr1p). Biochemical characterization, regulation bycopper, and physiologic role in copper uptake [J]. Journal of BiologicalChemistry,1994,269(41):25660-25667.
[61] JANDIAL D D, FARSHCHI-HEYDARI S, LARSON C A, et al. Enhanceddelivery of cisplatin to intraperitoneal ovarian carcinomas mediated by theeffects of bortezomib on the human copper transporter1[J]. Clinical cancerresearch,2009,15(2):553-560.
[62] PE A M M O, LEE J, THIELE D J. A delicate balance: homeostatic control ofcopper uptake and distribution [J]. The Journal of nutrition,1999,129(7):1251-1260.
[63] BELLEMARE D R, SHANER L, MORANO K A, et al. Ctr6, a VacuolarMembrane Copper Transporter inSchizosaccharomyces pombe [J]. Journal ofBiological Chemistry,2002,277(48):46676-46686.
[64] ZHOU B, GITSCHIER J. hCTR1: a human gene for copper uptake identifiedby complementation in yeast [J]. Proceedings of the National Academy ofSciences,1997,94(14):7481-7486.
[65] KLOMP A E M, TOPS B B J, VAN DENBERG I E T, et al. Biochemicalcharacterization and subcellular localization of human copper transporter1(hCTR1)[J]. Biochemical Journal,2002,364(Pt2):497-505.
[66]MARYON E, MOLLOY S, ZIMNICKA A, et al. Copper entry into human cells:progress and unanswered questions [J]. Biometals,2007,20(3):355-364.
[67] JIANG J, NADAS I A, KIM M A, et al. A Mets motif peptide found in coppertransport proteins selectively binds Cu (I) with methionine-only coordination[J]. Inorganic chemistry,2005,44(26):9787-9794.
[68] RUBINO J T, RIGGS-GELASCO P, FRANZ K J. Methionine motifs of coppertransport proteins provide general and flexible thioether-only binding sites forCu (I) and Ag (I)[J]. Journal of Biological Inorganic Chemistry,2010,15(7):1033-1049.
[69] PUIG S, LEE J, LAU M, et al. Biochemical and genetic analyses of yeast andhuman high affinity copper transporters suggest a conserved mechanism forcopper uptake [J]. Journal of Biological Chemistry,2002,277(29):26021-26030.
[70] EISSES J F, KAPLAN J H. The mechanism of copper uptake mediated byhuman CTR1[J]. Journal of Biological Chemistry,2005,280(44):37159-37168.
[71] HASSETT R, KOSMAN D J. Evidence for Cu (II) reduction as a component ofcopper uptake by Saccharomyces cerevisiae [J]. Journal of BiologicalChemistry,1995,270(1):128-134.
[72] DANCIS A, YUAN D S, HAILE D, et al. Molecular characterization of acopper transport protein in S. cerevisiae: an unexpected role for copper in irontransport [J]. Cell,1994,76(2):393-402.
[73] GEORGATSOU E, MAVROGIANNIS L A, FRAGIADAKIS G S, et al. Theyeast Fre1p/Fre2p cupric reductases facilitate copper uptake and are regulatedby the copper-modulated Mac1p activator [J]. Journal of Biological Chemistry,1997,272(21):13786-13792.
[74] RORABACHER D B. Electron transfer by copper centers [J]. Chemicalreviews,2004,104:651-697.
[75] COLMAN P, FREEMAN H, GUSS J, et al. X-ray crystal structure analysis ofplastocyanin at2.7resolution [J]. Nature,1978,272:319-324.
[76] NORRIS G E, ANDERSON B F, BAKER E N. Blue copper proteins. Thecopper site in azurin from Alcaligenes denitrificans [J]. Journal of the AmericanChemical Society,1986,108(10):2784-2785.
[77] ARNESANO F, BANCI L, BERTINI I, et al. Solution structure of the Cu (I)and apo forms of the yeast metallochaperone, Atx1[J]. Biochemistry,2001,40(6):1528-1539.
[78] ARNESANO F, BANCI L, BERTINI I, et al. Characterization of the bindinginterface between the copper chaperone Atx1and the first cytosolic domain ofCcc2ATPase [J]. Journal of Biological Chemistry,2001,276(44):41365-41376.
[79] SCHAFER F Q, BUETTNER G R. Redox environment of the cell as viewedthrough the redox state of the glutathione disulfide/glutathione couple [J]. FreeRadical Biology and Medicine,2001,30(11):1191-1212.
[80] DAVIS A V, O'HALLORAN T V. A place for thioether chemistry in cellularcopper ion recognition and trafficking [J]. Nature chemical biology,2008,4(3):148-151.
[81] KITTLESON J T, LOFTIN I R, HAUSRATH A C, et al. Periplasmicmetal-resistance protein CusF exhibits high affinity and specificity for both CuIand AgI [J]. Biochemistry,2006,45(37):11096-11102.
[82] ELAM J S, THOMAS S T, HOLLOWAY S P, et al. Copper chaperones [J].Advances in protein chemistry,2002,60:151-219.
[83] ZUIDERWEG E R P. Mapping protein-protein interactions in solution by NMRspectroscopy [J]. Biochemistry,2002,41(1):1-7.
[84] PELLECCHIA M, MONTGOMERY D L, STEVENS S Y, et al. Structuralinsights into substrate binding by the molecular chaperone DnaK [J]. naturestructural biology,2000,7(4):298-303.
[85]林东海,洪晶.用NMR技术研究蛋白质-配体相互作用[J].波谱学杂志,2005,22(003):321-341.
[86] AKKE M, CHAZIN W J. An open and shut case [J]. nature structural biology,2001,8(11):910-912.
[87] ISHIMA R, TORCHIA D A. Protein dynamics from NMR [J]. nature structuralbiology,2000,7(9):740-743.
[88]廖新丽,林东海.用异核多维NMR技术研究蛋白质动力学[J].波谱学杂志,2004,21(004):385-396.
[89] KAY L E. NMR studies of protein structure and dynamics [J]. Journal ofMagnetic Resonance,2005,173(2):193-207.
[90] BOEHR D D, DYSON H J, WRIGHT P E. An NMR perspective on enzymedynamics [J]. Chemical reviews,2006,106(8):3055-3079.
[91] KURLAND R J, MCGARVEY B R. Isotropic NMR shifts in transition metalcomplexes: the calculation of the Fermi contact and pseudocontact terms [J].Journal of Magnetic Resonance (1969),1970,2(3):286-301.
[92] ARNESANO F, BANCI L, PICCIOLI M. NMR structures of paramagneticmetalloproteins [J]. Quarterly Reviews of Biophysics,2005,38(02):167-219.
[93] SOLOMON I. Relaxation processes in a system of two spins [J]. PhysicalReview,1955,99(2):559-565.
[94] JENSEN M R, LED J J. Determination of the electron relaxation rates inparamagnetic metal complexes: applicability of available NMR methods [J].Journal of Magnetic Resonance,2004,167(2):169-177.
[95] BALAYSSAC S, BERTINI I, LUCHINAT C, et al.13C Direct Detected NMRIncreases the Detectability of Residual Dipolar Couplings [J]. Journal of theAmerican Chemical Society,2006,128(47):15042-15043.
[96] BABINI E, BERTINI I, CAPOZZI F, et al. Direct Carbon Detection inParamagnetic Metalloproteins To Further Exploit Pseudocontact ShiftRestraints [J]. Journal of the American Chemical Society,2004,126(34):10496-10497.
[97] BABAILOV S. Lanthanide paramagnetic probes for NMR spectroscopicstudies of molecular conformational dynamics in solution: Applications tomacrocyclic molecules [J]. Progress in Nuclear Magnetic ResonanceSpectroscopy,2008,52(1):1-21.
[98] FELLI I C, DESVAUX H, BODENHAUSEN G. Local mobility of15N labeledbiomolecules characterized through cross-correlation rates: Applications toparamagnetic proteins*[J]. Journal of Biomolecular NMR,1998,12(4):509-521.
[99] BERTINI I, BRYANT D A, CIURLI S, et al. Backbone dynamics ofplastocyanin in both oxidation states-Solution structure of the reduced formand comparison with the oxidized state [J]. Journal of Biological Chemistry,2001,276(50):47217-47226.
[100] OPELLA S, KIM Y, MCDONNELL P.[19] Experimental nuclear magneticresonance studies of membrane proteins [J]. Methods in enzymology,1994,239:536-560.
[101] SEDDON A M, CURNOW P, BOOTH P J. Membrane proteins, lipids anddetergents: not just a soap opera [J]. Biochimica et Biophysica Acta(BBA)-Biomembranes,2004,1666(1-2):105-117.
[102] ARORA A, TAMM L K. Biophysical approaches to membrane proteinstructure determination [J]. Current opinion in structural biology,2001,11(5):540-547.
[103] SAXENA V, WETLAUFER D. A new basis for interpreting the circulardichroic spectra of proteins [J]. Proceedings of the National Academy ofSciences,1971,68(5):969-972.
[104] BRAHMS S, BRAHMS J. Determination of protein secondary structure insolution by vacuum ultraviolet circular dichroism [J]. Journal of molecularbiology,1980,138(2):149-178.
[105] HENNESSEY JR J P, JOHNSON JR W C. Information content in thecircular dichroism of proteins [J]. Biochemistry,1981,20(5):1085-1094.
[106] PURCELL E M, TORREY H, POUND R V. Resonance absorption bynuclear magnetic moments in a solid [J]. Physical Review,1946,69(1-2):37-38.
[107] BLOCH F, HANSEN W, PACKARD M. Nuclear induction [J]. PhysicalReview,1946,70(7-8):460-474.
[108] ERNST R R, BODENHAUSEN G, WOKAUN A. Principles of nuclearmagnetic resonance in one and two dimensions [M]. Clarendon press Oxford,1987.
[109] WILLIAMSON M P, HAVEL T F, W THRICH K. Solution conformation ofproteinase inhibitor IIA from bull seminal plasma by1H nuclear magneticresonance and distance geometry [J]. Journal of molecular biology,1985,182(2):295-315.
[110] W THRICH K. The second decade-into the third millenium [J]. naturestructural biology,1998,5(7):492-495.
[111]毛希安.现代核磁共振实用技术及应用[M].科学技术文献出版社,2000.
[112]王大成,生物学.蛋白质工程[M].化学工业出版社现代生物技术与医药科技出版中心,2002.
[113] CHRISTENSEN J J, IZATT R M, HANSEN L D, et al. Entropy Titration. ACalorimetric Method for the Determination of ΔG, ΔH, and ΔS from a SingleThermometric Titration1a,b [J]. The Journal of Physical Chemistry,1966,70(6):2003-2010.
[114] IZATT R M, RYTTING J H, HANSEN L D, et al. Thermodynamics ofProton Dissociation in Dilute Aqueous Solution. V. An Entropy Titration Studyof Adenosine, Pentoses, Hexoses, and Related Compounds1a, b [J]. Journal ofthe American Chemical Society,1966,88(12):2641-2645.
[115] RONGTI C, ZONGXIN G, XUEMIN C. The Construction of a ConstantTemperature Environment-Continuous Titration Calorimeter and theImprovement of Thermogram Analysis [J]. Chemical Research In ChineseUniversities,1987,8(9):823-828.
[116]杨桦,王文清.量热滴定法测定苯丙氨酸,亮氨酸,蛋氨酸,色氨酸的热力学函数[J].物理化学学报,1989,5(005):583-586.
[117] SEELIG J. Titration calorimetry of lipid-peptide interactions [J].Biochimica et biophysica acta, MR Reviews on biomembranes,1997,1331(1):103-116.
[118] WENK M R, SEELIG J. Magainin2amide interaction with lipidmembranes: calorimetric detection of peptide binding and pore formation [J].Biochemistry,1998,37(11):3909-3916.
[119] STITES W E. Protein-protein interactions: interface structure, bindingthermodynamics, and mutational analysis [J]. Chemical reviews,1997,97(5):1233-1250.
[120] WIEPRECHT T, APOSTOLOV O, BEYERMANN M, et al.Thermodynamics of the [alpha]-helix-coil transition of amphipathic peptides ina membrane environment: implications for the peptide-membrane bindingequilibrium1[J]. Journal of molecular biology,1999,294(3):785-794.
[121] TODD M J, GOMEZ J. Enzyme kinetics determined using calorimetry: ageneral assay for enzyme activity?[J]. Analytical biochemistry,2001,296(2):179-187.
[122] LEAVITT S, FREIRE E. Direct measurement of protein binding energeticsby isothermal titration calorimetry [J]. Current opinion in structural biology,2001,11(5):560-566.
[123] CRAIK D J, WILCE J A. Studies of protein-ligand interactions by NMR [J].METHODS IN MOLECULAR BIOLOGY,1997,60:195-232.
[124] DAM T K, TORRES M, BREWER C F, et al. Isothermal titrationcalorimetry reveals differential binding thermodynamics of variableregion-identical antibodies differing in constant region for a univalent ligand [J].Journal of Biological Chemistry,2008,283(46):31366-31370.
[125] CHEN Z X, GUO G M, DENG S P. Isothermal Titration Calorimetry Studyof the Interaction of Sweeteners with Fullerenols as an Artificial Sweet TasteReceptor Model [J]. Journal of agricultural and food chemistry,2009,57(7):2945-2954.
[126] REYMOND C, BISAILLON M, PERREAULT J P. Monitoring of an RNAmultistep folding pathway by isothermal titration calorimetry [J]. Biophysicaljournal,2009,96(1):132-140.
[127] WANG S S S, LIN M S, CHEN S L, et al. Using isothermal titrationcalorimetry to real-time monitor the heat of metabolism: A case study usingPC12cells and Aβ (1–40)[J]. Colloids and Surfaces B: Biointerfaces,2011,83(2):307-312.
[128] DE PAULA W X, DENADAI M L, SANTORO M M, et al.Supramolecular interactions between losartan and hydroxypropyl-β-CD: ESImass-spectrometry, NMR techniques, phase solubility, isothermal titrationcalorimetry and anti-hypertensive studies [J]. International journal ofpharmaceutics,2011,404(1):116-123.
[129] HENZLER K, HAUPT B R, LAUTERBACH K, et al. Adsorption ofβ-Lactoglobulin on Spherical Polyelectrolyte Brushes: Direct Proof ofCounterion Release by Isothermal Titration Calorimetry [J]. Journal of theAmerican Chemical Society,2010,132(9):3159-3163.
[130] FREIRE E, MAYORGA O L, STRAUME M. Isothermal titrationcalorimetry [J]. Analytical chemistry,1990,62(18):950A-959A.
[1] SREERAMA N, WOODY R W. Estimation of protein secondary structure fromcircular dichroism spectra: comparison of CONTIN, SELCON, and CDSSTRmethods with an expanded reference set [J]. Analytical biochemistry,2000,287(2):252-260.
[2] GODDARD T, KNELLER D. Sparky3NMR software [J]. University ofCalifornia, San Francisco,2001.
[3] G NTERT P, MUMENTHALER C, W THRICH K. Torsion angle dynamics forNMR structure calculation with the new program D1[J]. Journal of molecularbiology,1997,273(1):283-298.
[4] KORADI R, BILLETER M, W THRICH K. MOLMOL: a program for displayand analysis of macromolecular structures [J]. Journal of molecular graphics,1996,14(1):51-55.
[1] LINDBERG M, GR SLUND A. The position of the cell penetrating peptidepenetratin in SDS micelles determined by NMR [J]. FEBS letters,2001,497(1):39-44.
[2] RUBINO J T, CHENKIN M P, KELLER M, et al. A comparison of methionine,histidine and cysteine in copper (I)-binding peptides reveals differences relevantto copper uptake by organisms in diverse environments [J]. Metallomics,2011,3(1):61-73.
[3] SHELLEY W B, SHELLEY E D, BURMEISTER V. Argyria: The intradermal[J]. Journal of the American Academy of Dermatology,1987,16(1):211-217.
[4] ARNESANO F, SCINTILLA S, NATILE G. Interaction between platinumcomplexes and a methionine motif found in copper transport proteins [J].Angewandte Chemie,2007,119(47):9220-9222.
[5] WANG X, DU X, LI H, et al. The Effect of the Extracellular Domain of HumanCopper Transporter (hCTR1) on Cisplatin Activation [J]. Angewandte ChemieInternational Edition,2011,50(12):2706-2711.
[6] LEE J, PE A M M O, NOSE Y, et al. Biochemical characterization of the humancopper transporter Ctr1[J]. Journal of Biological Chemistry,2002,277(6):4380-4387.
[2] MODAK S M, SAMPATH L, FOX JR C. Combined topical use of silversulfadiazine and antibiotics as a possible solution to bacterial resistance in burnwounds [J]. Journal of Burn Care&Research,1988,9(4):359-363.
[3] TROP M, NOVAK M, RODL S, et al. Silver-coated dressing acticoat causedraised liver enzymes and argyria-like symptoms in burn patient [J]. The Journalof trauma,2006,60(3):648-652.
[4]刘康时,江显异,赵英.银系无机抗菌剂作用机理的研究进展[J].佛山陶瓷,2001,11(56):1-5.
[5]陈四红,吕曼祺,张敬党, et al.含Cu抗菌不锈钢的微观组织及其抗菌性能[J].金属学报,2004,40(3):314-318.
[6]墙蔷,倪红卫,幸伟, et al.银的抗菌作用机理[J].武汉科技大学学报:自然科学版,2007,30(2):121-124.
[7] FENG Q, WU J, CHEN G, et al. A mechanistic study of the antibacterial effectof silver ions on Escherichia coli and Staphylococcus aureus [J]. Journal ofbiomedical materials research,2000,52(4):662-668.
[8] LING FENG Q, NAM KIM T, WU J, et al. Antibacterial effects of Ag-HApthin films on alumina substrates [J]. Thin Solid Films,1998,335(1-2):214-219.
[9]康湛莹,李瑞增.重金属离子杀菌作用的机理[J].哈尔滨科学技术大学学报,1995,19(003):103-106.
[10] LIAU S, READ D, PUGH W, et al. Interaction of silver nitrate with readilyidentifiable groups: relationship to the antibacterialaction of silver ions [J].Letters in Applied Microbiology,1997,25(4):279-283.
[11]余海霞,张泽强.戴银型抗菌累托石的制备及其性能[J].武汉化工学院学报,2003,25(1):46-48.
[12] INOUE Y, HOSHINO M, TAKAHASHI H, et al. Bactericidal activity ofAg–zeolite mediated by reactive oxygen species under aerated conditions [J].Journal of inorganic biochemistry,2002,92(1):37-42.
[13] DAVIES R L, ETRIS S F. The development and functions of silver in waterpurification and disease control [J]. Catalysis Today,1997,36(1):107-114.
[14] MIAO A J, SCHWEHR K A, XU C, et al. The algal toxicity of silverengineered nanoparticles and detoxification by exopolymeric substances [J].Environmental Pollution,2009,157(11):3034-3041.
[15] HARTFORD C E, ZIFFREN S E. The use of0.5%silver nitrate in burns:results in220patients [J]. The Journal of trauma,1972,12(8):682-688.
[16] FABREGA J, FAWCETT S R, RENSHAW J C, et al. Silver nanoparticle impacton bacterial growth: Effect of pH, concentration, and organic matter [J].Environmental science&technology,2009,43(19):7285-7290.
[17] BERTINATO J, CHEUNG L, HOQUE R, et al. Ctr1transports silver intomammalian cells [J]. Journal of Trace Elements in Medicine and Biology,2010,24(3):178-184.
[18] GULBRANSON S H, HUD J A, HANSEN R C. Argyria following the use ofdietary supplements containing colloidal silver protein [J]. Cutis,2000,66(5):373-376.
[19] SHELLEY W B, SHELLEY E D, BURMEISTER V. Argyria: The intradermal[J]. Journal of the American Academy of Dermatology,1987,16(1):211-217.
[20] BALDI C, MINOIA C, NUCCI A D, et al. Effects of silver in isolated rathepatocytes [J]. Toxicology letters,1988,41(3):261-268.
[21] SHINOGI M, MAEIZUMI S. Effect of preinduction of metallothionein ontissue distribution of silver and hepatic lipid peroxidation [J]. Biological&pharmaceutical bulletin,1993,16(4):372-374.
[22] HOLLINGER M A. Toxicological aspects of topical silver pharmaceuticals [J].CRC Critical Reviews in Toxicology,1996,26(3):255-260.
[23] GAMELLI R L, PAXTON T P, O'REILLY M. Bone marrow toxicity by silversulfadiazine [J]. Surgery, gynecology&obstetrics,1993,177(2):115-120.
[24] ZAPATA-SIRVENT R L, HANSBROUGH J F. Cytotoxicity to humanleukocytes by topical antimicrobial agents used for burn care [J]. The Journal ofburn care&rehabilitation,1993,14(2Pt1):132-140.
[25] HULTMAN P, ENESTR M S, TURLEY S, et al. Selective induction ofanti‐fibrillarin autoantibodies by silver nitrate in mice [J]. Clinical&Experimental Immunology,1994,96(2):285-291.
[26] STEFFENSEN I, MESNA O, ANDRUCHOW E, et al. Cytotoxicity andaccumulation of Hg, Ag, Cd, Cu, Pb and Zn in human peripheral T and Blymphocytes and monocytes in vitro [J]. General Pharmacology: The VascularSystem,1994,25(8):1621-1633.
[27] JANSSON G, HARMS-RINGDAHL M. Stimulating effects of mercuric-andsilver ions on the superoxide anion production in human polymorphonuclearleukocytes [J]. Free Radical Research,1993,18(2):87-98.
[28] SILVER S. Bacterial silver resistance: molecular biology and uses and misusesof silver compounds [J]. FEMS microbiology reviews,2003,27(2‐3):341-353.
[29] ROPER W. Toxicological profile for silver [J].Agency for Toxic Substances andDisease Registry, US Public Health Service, Atlanta, GA,1990.
[30] WAN A T, CONYERS R, COOMBS C J, et al. Determination of silver in blood,urine, and tissues of volunteers and burn patients [J]. Clinical chemistry,1991,37(10):1683-1687.
[31] CATSAKIS L, SULICA V. Allergy to silver amalgams [J]. Oral Surgery, OralMedicine, Oral Pathology,1978,46(3):371-375.
[32] SATO S, SUEKI H, NISHIJIMA A. Two unusual cases of argyria: theapplication of an improved tissue processing method for X-ray microanalysis ofselenium and sulphur in silver-laden granules [J]. British Journal ofDermatology,1999,140:158-163.
[33] SAINT S, VEENSTRA D L, SULLIVAN S D, et al. The potential clinical andeconomic benefits of silver alloy urinary catheters in preventing urinary tractinfection [J]. Archives of Internal Medicine,2000,160(17):2670-2675.
[34] RONGIOLETTI F, ROBERT E, BUFFA P, et al. Blue nevi-like dottedoccupational argyria [J]. Journal of the American Academy of Dermatology,1992,27(6Pt1):1015-1016.
[35] FURCHNER J, RICHMOND C, DRAKE G. Comparative metabolism ofradionuclides in mammals-IV. Retention of silver-110m in the mouse, rat,monkey, and dog [J]. Health physics,1968,15(6):505-514.
[36] KLEIN D A. Environmental Impacts of Artificial Ice Nucleating Agents.Dowden, Hutchinson&Ross [J]. Inc, Stroudburg, Pennsylvania,1978,169-175.
[37] ROSENMAN K, MOSS A, KON S. Argyria: clinical implications of exposureto silver nitrate and silver oxide [J]. Journal of Occupational and EnvironmentalMedicine,1979,21(6):430-435.
[38] SUE Y M, YU-YUN LEE J, WANG M C, et al. Generalized argyria in twochronic hemodialysis patients [J]. American journal of kidney diseases,2001,37(5):1048-1051.
[39] ROSENMAN K, SEIXAS N, JACOBS I. Potential nephrotoxic effects ofexposure to silver [J]. British journal of industrial medicine,1987,44(4):267-272.
[40] FRANCIS W. Health hazard from occupational exposure to metallic copper andsilver dust [J]. The American Industrial Hygiene Association Journal,1979,40(3):245-247.
[41] VENUGOPAL B, LUCKEY T. Metal toxicity in mammals.[J]. Chemicaltoxicity of metals and metalloids, Acedemic Press,1978,32-36.
[42] SHELLEY W B, SHELLEY E D, BURMEISTER V. Argyria: the intradermal"photograph", a manifestation of passive photosensitivity [J]. Journal of theAmerican Academy of Dermatology,1987,16(1):211-217.
[43] FUNG M C, BOWEN D L. Silver products for medical indications: risk-benefitassessment [J]. Clinical Toxicology,1996,34(1):119-126.
[44] PETRIS M J, MERCER J, CULVENOR J G, et al. Ligand-regulated transportof the Menkes copper P-type ATPase efflux pump from the Golgi apparatus tothe plasma membrane: a novel mechanism of regulated trafficking [J]. TheEMBO journal,1996,15(22):6084-6095.
[45] VERHEIJEN F W, BEERENS C, HAVELAAR A C, et al. Fibroblast silverloading for the diagnosis of Menkes disease [J]. Journal of medical genetics,1998,35(10):849-851.
[46] IBRICEVIC A, BRODY S L, YOUNGS W J, et al. ATP7B detoxifies silver inciliated airway epithelial cells [J]. Toxicology and applied pharmacology,2010,243(3):315-322.
[47] LEE J, PE A M M O, NOSE Y, et al. Biochemical characterization of the humancopper transporter Ctr1[J]. Journal of Biological Chemistry,2002,277(6):4380-4387.
[48] PETRIS M J, SMITH K, LEE J, et al. Copper-stimulated endocytosis anddegradation of the human copper transporter, hCtr1[J]. Journal of BiologicalChemistry,2003,278(11):9639-9646.
[49] KIM H, SON H Y, BAILEY S M, et al. Deletion of hepatic Ctr1reveals itsfunction in copper acquisition and compensatory mechanisms for copperhomeostasis [J]. American Journal of Physiology-Gastrointestinal and LiverPhysiology,2009,296(2): G356-G364.
[50] ZIMNICKA A M, MARYON E B, KAPLAN J H. Human copper transporterhCTR1mediates basolateral uptake of copper into enterocytes [J]. Journal ofBiological Chemistry,2007,282(36):26471-26480.
[51] BERTINATO J, SWIST E, PLOUFFE L, et al. Ctr2is partially localized to theplasma membrane and stimulates copper uptake in COS-7cells [J]. Biochem J,2008,409:731-740.
[52] ABADA P, HOWELL S B. Regulation of Cisplatin Cytotoxicity by Cu InfluxTransporters [J]. Metal-based drugs,2010,317581-317589.
[53] EISSES J F, KAPLAN J H. Molecular characterization of hCTR1, the humancopper uptake protein [J]. Journal of Biological Chemistry,2002,277(32):29162-29171.
[54] GITSCHIER J, MOFFAT B, REILLY D, et al. Solution structure of the fourthmetal-binding domain from the Menkes copper-transporting ATPase [J]. NatureStructural&Molecular Biology,1998,5(1):47-54.
[55] YAMAGUCHI Y, HEINY M, GITLIN J. Isolation and characterization of ahuman liver cDNA as a candidate gene for Wilson disease [J]. Biochemical andbiophysical research communications,1993,197(1):271-277.
[56] SCHAEFER M, HOPKINS R G, FAILLA M L, et al. Hepatocyte-specificlocalization and copper-dependent trafficking of the Wilson’s disease protein inthe liver [J]. American Journal of Physiology-Gastrointestinal and LiverPhysiology,1999,276(3): G639-G646.
[57]张英丽,鹿欣,丰有吉.铜离子转运蛋白家族与卵巢癌顺铂耐药关系的研究进展[J].现代妇产科进展,2007,16(5):388-390.
[58] LEE J, PROHASKA J R, DAGENAIS S L, et al. Isolation of a murine coppertransporter gene, tissue specific expression and functional complementation of ayeast copper transport mutant [J]. Gene,2000,254(1-2):87-96.
[59] PETRIS M J. The SLC31(Ctr) copper transporter family [J]. Pflügers ArchivEuropean Journal of Physiology,2004,447(5):752-755.
[60] DANCIS A, HAILE D, YUAN D S, et al. The Saccharomyces cerevisiaecopper transport protein (Ctr1p). Biochemical characterization, regulation bycopper, and physiologic role in copper uptake [J]. Journal of BiologicalChemistry,1994,269(41):25660-25667.
[61] JANDIAL D D, FARSHCHI-HEYDARI S, LARSON C A, et al. Enhanceddelivery of cisplatin to intraperitoneal ovarian carcinomas mediated by theeffects of bortezomib on the human copper transporter1[J]. Clinical cancerresearch,2009,15(2):553-560.
[62] PE A M M O, LEE J, THIELE D J. A delicate balance: homeostatic control ofcopper uptake and distribution [J]. The Journal of nutrition,1999,129(7):1251-1260.
[63] BELLEMARE D R, SHANER L, MORANO K A, et al. Ctr6, a VacuolarMembrane Copper Transporter inSchizosaccharomyces pombe [J]. Journal ofBiological Chemistry,2002,277(48):46676-46686.
[64] ZHOU B, GITSCHIER J. hCTR1: a human gene for copper uptake identifiedby complementation in yeast [J]. Proceedings of the National Academy ofSciences,1997,94(14):7481-7486.
[65] KLOMP A E M, TOPS B B J, VAN DENBERG I E T, et al. Biochemicalcharacterization and subcellular localization of human copper transporter1(hCTR1)[J]. Biochemical Journal,2002,364(Pt2):497-505.
[66]MARYON E, MOLLOY S, ZIMNICKA A, et al. Copper entry into human cells:progress and unanswered questions [J]. Biometals,2007,20(3):355-364.
[67] JIANG J, NADAS I A, KIM M A, et al. A Mets motif peptide found in coppertransport proteins selectively binds Cu (I) with methionine-only coordination[J]. Inorganic chemistry,2005,44(26):9787-9794.
[68] RUBINO J T, RIGGS-GELASCO P, FRANZ K J. Methionine motifs of coppertransport proteins provide general and flexible thioether-only binding sites forCu (I) and Ag (I)[J]. Journal of Biological Inorganic Chemistry,2010,15(7):1033-1049.
[69] PUIG S, LEE J, LAU M, et al. Biochemical and genetic analyses of yeast andhuman high affinity copper transporters suggest a conserved mechanism forcopper uptake [J]. Journal of Biological Chemistry,2002,277(29):26021-26030.
[70] EISSES J F, KAPLAN J H. The mechanism of copper uptake mediated byhuman CTR1[J]. Journal of Biological Chemistry,2005,280(44):37159-37168.
[71] HASSETT R, KOSMAN D J. Evidence for Cu (II) reduction as a component ofcopper uptake by Saccharomyces cerevisiae [J]. Journal of BiologicalChemistry,1995,270(1):128-134.
[72] DANCIS A, YUAN D S, HAILE D, et al. Molecular characterization of acopper transport protein in S. cerevisiae: an unexpected role for copper in irontransport [J]. Cell,1994,76(2):393-402.
[73] GEORGATSOU E, MAVROGIANNIS L A, FRAGIADAKIS G S, et al. Theyeast Fre1p/Fre2p cupric reductases facilitate copper uptake and are regulatedby the copper-modulated Mac1p activator [J]. Journal of Biological Chemistry,1997,272(21):13786-13792.
[74] RORABACHER D B. Electron transfer by copper centers [J]. Chemicalreviews,2004,104:651-697.
[75] COLMAN P, FREEMAN H, GUSS J, et al. X-ray crystal structure analysis ofplastocyanin at2.7resolution [J]. Nature,1978,272:319-324.
[76] NORRIS G E, ANDERSON B F, BAKER E N. Blue copper proteins. Thecopper site in azurin from Alcaligenes denitrificans [J]. Journal of the AmericanChemical Society,1986,108(10):2784-2785.
[77] ARNESANO F, BANCI L, BERTINI I, et al. Solution structure of the Cu (I)and apo forms of the yeast metallochaperone, Atx1[J]. Biochemistry,2001,40(6):1528-1539.
[78] ARNESANO F, BANCI L, BERTINI I, et al. Characterization of the bindinginterface between the copper chaperone Atx1and the first cytosolic domain ofCcc2ATPase [J]. Journal of Biological Chemistry,2001,276(44):41365-41376.
[79] SCHAFER F Q, BUETTNER G R. Redox environment of the cell as viewedthrough the redox state of the glutathione disulfide/glutathione couple [J]. FreeRadical Biology and Medicine,2001,30(11):1191-1212.
[80] DAVIS A V, O'HALLORAN T V. A place for thioether chemistry in cellularcopper ion recognition and trafficking [J]. Nature chemical biology,2008,4(3):148-151.
[81] KITTLESON J T, LOFTIN I R, HAUSRATH A C, et al. Periplasmicmetal-resistance protein CusF exhibits high affinity and specificity for both CuIand AgI [J]. Biochemistry,2006,45(37):11096-11102.
[82] ELAM J S, THOMAS S T, HOLLOWAY S P, et al. Copper chaperones [J].Advances in protein chemistry,2002,60:151-219.
[83] ZUIDERWEG E R P. Mapping protein-protein interactions in solution by NMRspectroscopy [J]. Biochemistry,2002,41(1):1-7.
[84] PELLECCHIA M, MONTGOMERY D L, STEVENS S Y, et al. Structuralinsights into substrate binding by the molecular chaperone DnaK [J]. naturestructural biology,2000,7(4):298-303.
[85]林东海,洪晶.用NMR技术研究蛋白质-配体相互作用[J].波谱学杂志,2005,22(003):321-341.
[86] AKKE M, CHAZIN W J. An open and shut case [J]. nature structural biology,2001,8(11):910-912.
[87] ISHIMA R, TORCHIA D A. Protein dynamics from NMR [J]. nature structuralbiology,2000,7(9):740-743.
[88]廖新丽,林东海.用异核多维NMR技术研究蛋白质动力学[J].波谱学杂志,2004,21(004):385-396.
[89] KAY L E. NMR studies of protein structure and dynamics [J]. Journal ofMagnetic Resonance,2005,173(2):193-207.
[90] BOEHR D D, DYSON H J, WRIGHT P E. An NMR perspective on enzymedynamics [J]. Chemical reviews,2006,106(8):3055-3079.
[91] KURLAND R J, MCGARVEY B R. Isotropic NMR shifts in transition metalcomplexes: the calculation of the Fermi contact and pseudocontact terms [J].Journal of Magnetic Resonance (1969),1970,2(3):286-301.
[92] ARNESANO F, BANCI L, PICCIOLI M. NMR structures of paramagneticmetalloproteins [J]. Quarterly Reviews of Biophysics,2005,38(02):167-219.
[93] SOLOMON I. Relaxation processes in a system of two spins [J]. PhysicalReview,1955,99(2):559-565.
[94] JENSEN M R, LED J J. Determination of the electron relaxation rates inparamagnetic metal complexes: applicability of available NMR methods [J].Journal of Magnetic Resonance,2004,167(2):169-177.
[95] BALAYSSAC S, BERTINI I, LUCHINAT C, et al.13C Direct Detected NMRIncreases the Detectability of Residual Dipolar Couplings [J]. Journal of theAmerican Chemical Society,2006,128(47):15042-15043.
[96] BABINI E, BERTINI I, CAPOZZI F, et al. Direct Carbon Detection inParamagnetic Metalloproteins To Further Exploit Pseudocontact ShiftRestraints [J]. Journal of the American Chemical Society,2004,126(34):10496-10497.
[97] BABAILOV S. Lanthanide paramagnetic probes for NMR spectroscopicstudies of molecular conformational dynamics in solution: Applications tomacrocyclic molecules [J]. Progress in Nuclear Magnetic ResonanceSpectroscopy,2008,52(1):1-21.
[98] FELLI I C, DESVAUX H, BODENHAUSEN G. Local mobility of15N labeledbiomolecules characterized through cross-correlation rates: Applications toparamagnetic proteins*[J]. Journal of Biomolecular NMR,1998,12(4):509-521.
[99] BERTINI I, BRYANT D A, CIURLI S, et al. Backbone dynamics ofplastocyanin in both oxidation states-Solution structure of the reduced formand comparison with the oxidized state [J]. Journal of Biological Chemistry,2001,276(50):47217-47226.
[100] OPELLA S, KIM Y, MCDONNELL P.[19] Experimental nuclear magneticresonance studies of membrane proteins [J]. Methods in enzymology,1994,239:536-560.
[101] SEDDON A M, CURNOW P, BOOTH P J. Membrane proteins, lipids anddetergents: not just a soap opera [J]. Biochimica et Biophysica Acta(BBA)-Biomembranes,2004,1666(1-2):105-117.
[102] ARORA A, TAMM L K. Biophysical approaches to membrane proteinstructure determination [J]. Current opinion in structural biology,2001,11(5):540-547.
[103] SAXENA V, WETLAUFER D. A new basis for interpreting the circulardichroic spectra of proteins [J]. Proceedings of the National Academy ofSciences,1971,68(5):969-972.
[104] BRAHMS S, BRAHMS J. Determination of protein secondary structure insolution by vacuum ultraviolet circular dichroism [J]. Journal of molecularbiology,1980,138(2):149-178.
[105] HENNESSEY JR J P, JOHNSON JR W C. Information content in thecircular dichroism of proteins [J]. Biochemistry,1981,20(5):1085-1094.
[106] PURCELL E M, TORREY H, POUND R V. Resonance absorption bynuclear magnetic moments in a solid [J]. Physical Review,1946,69(1-2):37-38.
[107] BLOCH F, HANSEN W, PACKARD M. Nuclear induction [J]. PhysicalReview,1946,70(7-8):460-474.
[108] ERNST R R, BODENHAUSEN G, WOKAUN A. Principles of nuclearmagnetic resonance in one and two dimensions [M]. Clarendon press Oxford,1987.
[109] WILLIAMSON M P, HAVEL T F, W THRICH K. Solution conformation ofproteinase inhibitor IIA from bull seminal plasma by1H nuclear magneticresonance and distance geometry [J]. Journal of molecular biology,1985,182(2):295-315.
[110] W THRICH K. The second decade-into the third millenium [J]. naturestructural biology,1998,5(7):492-495.
[111]毛希安.现代核磁共振实用技术及应用[M].科学技术文献出版社,2000.
[112]王大成,生物学.蛋白质工程[M].化学工业出版社现代生物技术与医药科技出版中心,2002.
[113] CHRISTENSEN J J, IZATT R M, HANSEN L D, et al. Entropy Titration. ACalorimetric Method for the Determination of ΔG, ΔH, and ΔS from a SingleThermometric Titration1a,b [J]. The Journal of Physical Chemistry,1966,70(6):2003-2010.
[114] IZATT R M, RYTTING J H, HANSEN L D, et al. Thermodynamics ofProton Dissociation in Dilute Aqueous Solution. V. An Entropy Titration Studyof Adenosine, Pentoses, Hexoses, and Related Compounds1a, b [J]. Journal ofthe American Chemical Society,1966,88(12):2641-2645.
[115] RONGTI C, ZONGXIN G, XUEMIN C. The Construction of a ConstantTemperature Environment-Continuous Titration Calorimeter and theImprovement of Thermogram Analysis [J]. Chemical Research In ChineseUniversities,1987,8(9):823-828.
[116]杨桦,王文清.量热滴定法测定苯丙氨酸,亮氨酸,蛋氨酸,色氨酸的热力学函数[J].物理化学学报,1989,5(005):583-586.
[117] SEELIG J. Titration calorimetry of lipid-peptide interactions [J].Biochimica et biophysica acta, MR Reviews on biomembranes,1997,1331(1):103-116.
[118] WENK M R, SEELIG J. Magainin2amide interaction with lipidmembranes: calorimetric detection of peptide binding and pore formation [J].Biochemistry,1998,37(11):3909-3916.
[119] STITES W E. Protein-protein interactions: interface structure, bindingthermodynamics, and mutational analysis [J]. Chemical reviews,1997,97(5):1233-1250.
[120] WIEPRECHT T, APOSTOLOV O, BEYERMANN M, et al.Thermodynamics of the [alpha]-helix-coil transition of amphipathic peptides ina membrane environment: implications for the peptide-membrane bindingequilibrium1[J]. Journal of molecular biology,1999,294(3):785-794.
[121] TODD M J, GOMEZ J. Enzyme kinetics determined using calorimetry: ageneral assay for enzyme activity?[J]. Analytical biochemistry,2001,296(2):179-187.
[122] LEAVITT S, FREIRE E. Direct measurement of protein binding energeticsby isothermal titration calorimetry [J]. Current opinion in structural biology,2001,11(5):560-566.
[123] CRAIK D J, WILCE J A. Studies of protein-ligand interactions by NMR [J].METHODS IN MOLECULAR BIOLOGY,1997,60:195-232.
[124] DAM T K, TORRES M, BREWER C F, et al. Isothermal titrationcalorimetry reveals differential binding thermodynamics of variableregion-identical antibodies differing in constant region for a univalent ligand [J].Journal of Biological Chemistry,2008,283(46):31366-31370.
[125] CHEN Z X, GUO G M, DENG S P. Isothermal Titration Calorimetry Studyof the Interaction of Sweeteners with Fullerenols as an Artificial Sweet TasteReceptor Model [J]. Journal of agricultural and food chemistry,2009,57(7):2945-2954.
[126] REYMOND C, BISAILLON M, PERREAULT J P. Monitoring of an RNAmultistep folding pathway by isothermal titration calorimetry [J]. Biophysicaljournal,2009,96(1):132-140.
[127] WANG S S S, LIN M S, CHEN S L, et al. Using isothermal titrationcalorimetry to real-time monitor the heat of metabolism: A case study usingPC12cells and Aβ (1–40)[J]. Colloids and Surfaces B: Biointerfaces,2011,83(2):307-312.
[128] DE PAULA W X, DENADAI M L, SANTORO M M, et al.Supramolecular interactions between losartan and hydroxypropyl-β-CD: ESImass-spectrometry, NMR techniques, phase solubility, isothermal titrationcalorimetry and anti-hypertensive studies [J]. International journal ofpharmaceutics,2011,404(1):116-123.
[129] HENZLER K, HAUPT B R, LAUTERBACH K, et al. Adsorption ofβ-Lactoglobulin on Spherical Polyelectrolyte Brushes: Direct Proof ofCounterion Release by Isothermal Titration Calorimetry [J]. Journal of theAmerican Chemical Society,2010,132(9):3159-3163.
[130] FREIRE E, MAYORGA O L, STRAUME M. Isothermal titrationcalorimetry [J]. Analytical chemistry,1990,62(18):950A-959A.
[1] SREERAMA N, WOODY R W. Estimation of protein secondary structure fromcircular dichroism spectra: comparison of CONTIN, SELCON, and CDSSTRmethods with an expanded reference set [J]. Analytical biochemistry,2000,287(2):252-260.
[2] GODDARD T, KNELLER D. Sparky3NMR software [J]. University ofCalifornia, San Francisco,2001.
[3] G NTERT P, MUMENTHALER C, W THRICH K. Torsion angle dynamics forNMR structure calculation with the new program D1[J]. Journal of molecularbiology,1997,273(1):283-298.
[4] KORADI R, BILLETER M, W THRICH K. MOLMOL: a program for displayand analysis of macromolecular structures [J]. Journal of molecular graphics,1996,14(1):51-55.
[1] LINDBERG M, GR SLUND A. The position of the cell penetrating peptidepenetratin in SDS micelles determined by NMR [J]. FEBS letters,2001,497(1):39-44.
[2] RUBINO J T, CHENKIN M P, KELLER M, et al. A comparison of methionine,histidine and cysteine in copper (I)-binding peptides reveals differences relevantto copper uptake by organisms in diverse environments [J]. Metallomics,2011,3(1):61-73.
[3] SHELLEY W B, SHELLEY E D, BURMEISTER V. Argyria: The intradermal[J]. Journal of the American Academy of Dermatology,1987,16(1):211-217.
[4] ARNESANO F, SCINTILLA S, NATILE G. Interaction between platinumcomplexes and a methionine motif found in copper transport proteins [J].Angewandte Chemie,2007,119(47):9220-9222.
[5] WANG X, DU X, LI H, et al. The Effect of the Extracellular Domain of HumanCopper Transporter (hCTR1) on Cisplatin Activation [J]. Angewandte ChemieInternational Edition,2011,50(12):2706-2711.
[6] LEE J, PE A M M O, NOSE Y, et al. Biochemical characterization of the humancopper transporter Ctr1[J]. Journal of Biological Chemistry,2002,277(6):4380-4387.