参考文献:1. Florkin M, Stotz EH: Enzyme Nomenclature. / Comprehensive Biochemistry 1973., 13: 2. Cheek S, Zhang H, Grishin NV: Sequence and structure classification of kinases. / J Mol Biol 2002, 320:855-81. href="http://dx.doi.org/10.1016/S0022-2836(02)00538-7">CrossRef 3. Cheek S, Ginalski K, Zhang H, Grishin NV: A comprehensive update of the sequence and structure classification of kinases. / BMC Struc Biol 2005,5(6):1-9. 4. Wiberg KB: The deuterium isotope effect. / Chem Rev 1955, 55:713-43. href="http://dx.doi.org/10.1021/cr50004a004">CrossRef 5. Carey FA, Sundberg RJ: / Advanced organic chemistry. Part A. Structure and Mechanisms. Plenum Press NewYork; 6. Buss KA, Cooper DC, Ingram-Smith C, Ferry JG, Sanders DA, Hanson MS: Urkinase: Structure of acetate kinase, a member of the ASHKA superfamily of phosphotransferases. / J Bacteriol 2001, 183:680-86. href="http://dx.doi.org/10.1128/JB.183.2.680-686.2001">CrossRef 7. Gorrell A, Ferry JG: Investigation of theMethanosarcina thermophilaacetate kinase mechanism by flourescence quenching. / Biochemistry 2007, 46:14170-4176. href="http://dx.doi.org/10.1021/bi701292a">CrossRef 8. Levitzki A, Stallcup WB, Koschland DE Jr: Half-of-sites reactivity and the conformational states of cytidine triphosphate synthetase. / Biochemistry 1971, 10:3371-378. href="http://dx.doi.org/10.1021/bi00794a009">CrossRef 9. Hill TL: Unsymmetrical and conserted examples of the effect of enzyme-enzyme interactions on the steady-state enzyme kinetics. / Proc Natl Acad Sci USA 1978, 75:1101-105. href="http://dx.doi.org/10.1073/pnas.75.3.1101">CrossRef 10. Schulzc IT, Colowick SP: The modification of yeast hexokinases by proteases and its relationship to the dissociation of hexokinase into subunits. / J Biol Chem 1969, 244:2306-316. 11. Easterby JS, Rosemeyer MA: Purification and subunit interactions of yeast hexokinase. / Eur J Biochem 1972, 2:241-52. href="http://dx.doi.org/10.1111/j.1432-1033.1972.tb01907.x">CrossRef 12. Derechin M, Rustum YM, Barnard EA: Dissociation of yeast hexokinase under the influence of substrates. / Biochemistry 1972, 11:1793-797. href="http://dx.doi.org/10.1021/bi00760a009">CrossRef 13. Schmidt JJ, Colowick SP: Purification and serological comparison of the yeast hexokinases P-I and P-II. / Arch Biochem Biophys 1973, 158:451-57. href="http://dx.doi.org/10.1016/0003-9861(73)90536-5">CrossRef 14. Hoggett JG, Kellett GL: Yeast hexokinase: Substrate-induced association-dissociation reactions in the binding of glucose to hexokinase P-II. / Eur J Biochem 1976, 66:65-7. href="http://dx.doi.org/10.1111/j.1432-1033.1976.tb10426.x">CrossRef 15. Bennett WS Jr, Steitz TA: Glucose-induced conformational changes in yeast hexokinase. / Proc Natl Acad Sci USA 1978, 75:4848-852. href="http://dx.doi.org/10.1073/pnas.75.10.4848">CrossRef 16. Katzen HM, Schimke RT: Multiple forms of hexokinase in the rat: tissue distribution, age dependency, and properties. / Proc Natl Acad Sci USA 1965, 54:1218-225. href="http://dx.doi.org/10.1073/pnas.54.4.1218">CrossRef 17. Steitz TA, Anderson WF, Fletterick RJ, Anderson CM: High resolution crystal structures of yeast hexokinase complexes with substrates, activators and inhibitors. / J Biol Chem 1977, 252:4494-500. 18. Anderson CM, Stenkamp RE, Steitz TA: Sequencing a protein by X-ray crystallography: II, Refinement of yeast hexokinase B co-ordinates and sequence at 2.1 ? resolution. / J Mol Biol 1978, 123:15-3. href="http://dx.doi.org/10.1016/0022-2836(78)90374-1">CrossRef 19. Anderson CM, Stenkamp RE, McDonald RC, Steitz TA: A refind model of the sugar binding site of yeast hexokinase B. / J Mol Biol 1978, 123:207-19. href="http://dx.doi.org/10.1016/0022-2836(78)90321-2">CrossRef 20. Bennett WS Jr, Steitz TA: Glucose-induced conformational change in yeast hexokinase. / Proc Natl Acad Sci USA 1978, 75:4848-852. href="http://dx.doi.org/10.1073/pnas.75.10.4848">CrossRef 21. Bennett WS Jr, Steitz TA: Structure of a complex between yeast hexokinase A and glucose: II. Detailed comparisons of conformation and active site configuration with the native hexokinase B monomer and dimer. / J Mol Biol 1980, 140:211-30. href="http://dx.doi.org/10.1016/0022-2836(80)90103-5">CrossRef 22. Shoham M, Steitz TA: The 6-hydroxymethyl group of a hexose is essential for the substrate-induced closure of the cleft in hexokinase. / Biochem Biophys Acta 1982, 705:380-84. href="http://dx.doi.org/10.1016/0167-4838(82)90260-6">CrossRef 23. Shill JP, Peters BA, Neet KE: Monomer-dimer equilbriums of yeast hexokinase during reacting enzyme sedimentation. / Biochemistry 1974, 13:3864-871. href="http://dx.doi.org/10.1021/bi00716a007">CrossRef 24. Womack F, Colowick SP: Catalytic activity with associated and dissociated forms of the yeast hexokinases. / Arch Biochmem Biophys 1978, 191:742-47. href="http://dx.doi.org/10.1016/0003-9861(78)90415-0">CrossRef 25. Mayes EL, Hoggett JG, Kellett GL: The binding of glucose to native and proteolytically modified yeast hexokinase PI. / Eur J Biochem 1983, 133:127-34. href="http://dx.doi.org/10.1111/j.1432-1033.1983.tb07437.x">CrossRef 26. Tickner EL, Hoggett JG, Kellett GL: The cooperative binding of glucose to yeast hexokinase PI dimer. / Biochem Biophys Res Commun 1976, 72:808-15. href="http://dx.doi.org/10.1016/S0006-291X(76)80205-7">CrossRef 27. Haslam E: / Shikimic Acid: Metabolism and Metabolites. Wiley: Chichester; 1993. 28. Vonrhein C, Schlauderer GJ, Schulz GF: Movie of the structural changes during a catalytic cycle of nucleoside monophosphate kinases. / Structure 1995, 3:483-90. href="http://dx.doi.org/10.1016/S0969-2126(01)00181-2">CrossRef 29. Gu Y, Reshetnikova L, Li Y, Wu Y, Yan H, Singh S, Ji X: Crystal Structure of shikimate kinase fromMycobacterium tuberculosisreveals the dynamic role of the LID domain in catalysis. / J Mol Biol 2002, 319:779-89. href="http://dx.doi.org/10.1016/S0022-2836(02)00339-X">CrossRef 30. Goldhammer AR, Paradies HH: Phosphofructokinase: structure and function. In / Current Topics in Cellular Regulation. Edited by: Horecker BL, Stadtman ER. Academic Press: New York; 1979:109-41. 31. Valdez BC, French BA, Younathan ES, Chang SH: Site-directed mutagenesis inBacillus stearothermophilusfructose-6-phosphate 1-kinase. / J Biol Chem 1989, 264:131-35. 32. Shapiro BM, Stadman ER: The regulation of glutamine synthesis in microorganisms. / Ann Rev Microbiol 1970, 24:501-24. href="http://dx.doi.org/10.1146/annurev.mi.24.100170.002441">CrossRef 33. Stadtman ER, Ginsburg A: / The Enzymes, vol 10, ed. Edited by: Boyer PD. Academic Press: New York; 1974:755-07. 34. Brown JR, Masuchi Y, Robb FT, Doolittle WF: Evolutionary relationships of bacterial and archaeal glutamine synthetase genes. / J Mol Evol 1994, 38:566-76. href="http://dx.doi.org/10.1007/BF00175876">CrossRef 35. Tyler B: Regulation of the assimilation of nitrogen compounds. / Ann Rev Biochem 1978, 47:1127-162. href="http://dx.doi.org/10.1146/annurev.bi.47.070178.005403">CrossRef 36. Gaillardin CM, Magasanik B: Involvement of the product of theglnFgene in the autogenous regulation of glutamine synthetase formation inKlebsiella aerogenes. / J Bacteriol 1978, 133:1329-338. 37. Foor F, Jannsen KA, Magasanik B: Regulation of synthesis of glutamine synthetase by adenylylated glutamine synthetase. / Proc Natl Acad Sci USA 1975, 75:4844-848. href="http://dx.doi.org/10.1073/pnas.72.12.4844">CrossRef 38. Janssen KA, Magasanik B: Glutamine synthetase ofKlebsiella aerogenes: genetic and physiological properties of mutants in the adenylylation system. / J Bacteriol 1977, 129:993-000. 39. Senior PJ: Regulation of nitrogen metabolism inEscherichia coliandKlebsiella aerogenes: studies with the continuous-culture technique. / J Bacteriol 1975, 123:407-18. 40. Ginsberg A, Stadtman ER: / Enzymes of Glutamine Metabolism. Edited by: Prusiner SR, Stadman ER. Academic Press, New York; 1973:9-4. 41. Wolhueter RM, Schutt H, Holzer H: / Enzymes of Glutamine Metabolism. Edited by: Prusiner SR, Stadman ER. Academic Press, New York; 1973:45-1. 42. Bender RA, Janssen KA, Resnick AD, Blumenberg M, Foor F, Magasanik B: Biochemical parameters of glutamine synthetase fromKlebsiella aerogenes. / J Bacteriol 1977, 129:1001-009. 43. Bloom FR, Streicher SL, Tyler B: Regulation of enzyme synthesis by glutamine synthetase ofSalmonella typhimurium: a factor in addition to glutamine synthetase is required for activation of enzyme formation. / J Bacteriol 1977, 130:983-90. 44. Holzer H, Schutt H, Ma?ek Z, Mecke D: Regulation of two forms of glutamine synthetase inEscherichia coliby the ammonium content of the growth medium. / Proc Natl Acad Sci USA 1968, 60:721-24. href="http://dx.doi.org/10.1073/pnas.60.2.721">CrossRef 45. Woolfolk CA, Shapiro B, Stadtman ER: Regulation of glutamine synthetase I. Purification and properties of glutamine synthetase fromEscherichia coli. / Arch Biochem Biophys 1966, 116:177-92. href="http://dx.doi.org/10.1016/0003-9861(66)90026-9">CrossRef 46. Kustu SG, McKereghan K: Mutations affecting glutamine synthetase activity inSalmonella typhimurium. / J Bacteriol 1975, 122:1006-016. 47. Shirakihara Y, Evans PR: Crystal structure of the complex of phosphofructokinase from Escherichia coli with its reaction products. / J Mol Biol 1988, 204:973-94. href="http://dx.doi.org/10.1016/0022-2836(88)90056-3">CrossRef 48. Rypniewski WR, Evans PR: Crystal structure of unliganded phosphofructokinase from Escherichia coli. / J Mol Biol 1989, 207:805-21. href="http://dx.doi.org/10.1016/0022-2836(89)90246-5">CrossRef 49. Schirmer T, Evans PR: Structural basis of the allosteric behaviour of phosphofructokinase. / Nature 1990, 343:140-45. href="http://dx.doi.org/10.1038/343140a0">CrossRef 50. Heller S: 1H NMR studies on deuterium - hydrogen exchange at C-5 in uridines. / Biochem Biophys Res Commun 1968, 32:998-001. href="http://dx.doi.org/10.1016/0006-291X(68)90127-7">CrossRef 51. Livramento J, Thomas GJ Jr: Detection of hydrogen deuterium exchange in purines by laser-raman spectroscopy. Adenosine 5'-monophosphate and polyriboadenylic acid. / J Amer Chem Soc 1974, 96:6529-531. href="http://dx.doi.org/10.1021/ja00827a054">CrossRef 52. Thomas GJ, Livramento J: Kinetics of hydrogen-deuterium exchange in adenosine 5'-monophosphate, adenosine 3':5'-monophosphate and poly(riboadenylic acid) determined by laser-raman spectroscopy. / Biochemistry 1975, 14:5210-218. href="http://dx.doi.org/10.1021/bi00694a030">CrossRef 53. Perfil'eva EA, Khropov Yu V, Khachatryan L, Bulargina TV, Baranova LA, Gulyaev NN, Libinzon RE, Severin ES: Adenylate cyclase from rabbit heart: investigation of substrate-binding site. / Biokhimiia 1981, 46:1127-133. 54. Baranova LA, Grivennikov IA, Gulyaev NN: Interaction of N1-, N6- N8-substituted derivatives of adenosine-5'-triphosphate with the catalytic subunit of cAMP-dependent protein kinase from rabbit skeletal muscles. / Biokhimiia 1982, 47:1534-541. 55. Saidenberg DM, Passarelli AW, Rodrigues AV, Basso LA, Santos DS, Palma MS: Shikimate kinase (EC 2.7.171) fromMycobacteriumtuberculosis: Kinetics and structural dynamics of a potential molecular target for drug development. / Curr Med Chem 2011, 47:1299-310. href="http://dx.doi.org/10.2174/092986711795029500">CrossRef 56. Laemmli UK: Cleavage of structural proteins during the assembly of the head of bacteriophage T4. / Nature 1970, 227:680-85. href="http://dx.doi.org/10.1038/227680a0">CrossRef
作者单位:Colin P Kenyon (1) Anjo Steyn (1) Robyn L Roth (1) Paul A Steenkamp (1) Thokozani C Nkosi (1) Lyndon C Oldfield (1)
1. CSIR, Biosciences, Meiring Naude Road, Pretoria, 0001, Gauteng, South Africa
文摘
Background The kinome comprises functionally diverse enzymes, with the current classification indicating very little about the extent of conserved regulatory mechanisms associated with phosphoryl transfer. The apparent K m of the kinases ranges from less than 0.4 μM to in excess of 1000 μM for ATP. It is not known how this diverse range of enzymes mechanistically achieves the regulation of catalysis via an affinity range for ATP varying by three-orders of magnitude. Results We have demonstrated a previously undiscovered mechanism in kinase and synthetase enzymes where the overall rate of reaction is regulated via the C8-H of ATP. Using ATP deuterated at the C8 position (C8D-ATP) as a molecular probe it was shown that the C8-H plays a direct role in the regulation of the overall rate of reaction in a range of kinase and synthetase enzymes. Using comparative studies on the effect of the concentration of ATP and C8D-ATP on the activity of the enzymes we demonstrated that not only did C8D-ATP give a kinetic isotope effect (KIE) but the KIE's obtained are clearly not secondary KIE effects as the magnitude of the KIE in all cases was at least 2 fold and in most cases in excess of 7 fold. Conclusions Kinase and synthetase enzymes utilise C8D-ATP in preference to non-deuterated ATP. The KIE obtained at low ATP concentrations is clearly a primary KIE demonstrating strong evidence that the bond to the isotopically substituted hydrogen is being broken. The effect of the ATP concentration profile on the KIE was used to develop a model whereby the C8H of ATP plays a role in the overall regulation of phosphoryl transfer. This role of the C8H of ATP in the regulation of substrate binding appears to have been conserved in all kinase and synthetase enzymes as one of the mechanisms associated with binding of ATP. The induction of the C8H to be labile by active site residues coordinated to the ATP purine ring may play a significant role in explaining the broad range of K m associated with kinase enzymes.