Backbone 1H, 13C, and 15N chemical shift assignment for HIV-1 protease subtypes and multi-drug resistant variant MDR 769

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• 作者：Xi Huang (1)
  Ian Mitchelle S. de Vera (1)
  Angelo M. Veloro (1)
  James R. Rocca (2)
  Carlos Simmerling (3)
  Ben M. Dunn (4)
  Gail E. Fanucci (1)
  
• 关键词：HIV ; 1 protease ; Naturally occurring polymorphism ; Multi ; drug resistance ; Resonance assignments
• 刊名：Biomolecular NMR Assignments
• 出版年：2013
• 出版时间：October 2013
• 年：2013
• 卷：7
• 期：2
• 页码：199-202
• 全文大小：514KB
• 参考文献：1. Ashorn P, McQuade TJ, Thaisrivongs S, Tomasselli AG, Tarpley WG, Moss B (1991) An inhibitor of the protease blocks maturation of human and simian immunodeficiency viruses and spread of infection. Proc Natl Acad Sci USA 87:7472鈥?476 CrossRef
  2. Delaglio F, Grzesiek S, Vuister GW, Zhu G, Pfiefer J, Bax A (1995) NMRPipe: a multidimensional spectral processing system based on UNIX pipes. J Biomol NMR 6:277鈥?93 CrossRef
  3. Freedberg DI, Ishima R, Jacob J, Wang YX, Kustanovich I, Louis JM, Torchia DA (2002) Rapid structural fluctuations of the free HIV protease flaps in solution: relationship to crystal structures and comparison with predictions of dynamics calculations. Protein Sci 11:221鈥?32 CrossRef
  4. Galiano L, Ding F, Veloro AM, Blackburn ME, Simmerling C, Fanucci GE (2009) Drug pressure selected mutations in HIV-1 protease alter flap conformations. J Am Chem Soc 131:430鈥?31 CrossRef
  5. Kear JL, Blackburn ME, Veloro AM, Dunn BM, Fanucci GE (2009) Subtype polymorphisms among HIV-1 protease variants confer altered flap conformations and flexibility. J Am Chem Soc 131:14650鈥?4651 CrossRef
  6. Longsdon BC, Vickrey JF, Martin P, Proteasa G, Koepke JI, Terlecky SR, Wawrzak Z, Winters MA, Merigan TC, Kovari LC (2004) Crystal structures of a multidrug-resistant human immunodeficiency virus type 1 protease reveal an expanded active-site cavity. J Virology 78:3123鈥?132 CrossRef
  7. Mildner AM, Rothrock DJ, Leone JW, Bannow CA, Lull JM, Reardon IM, Sarcich JL, Howe WJ, Tomich CS, Smith CW (1994) The HIV-1 protease as enzyme and substrate: mutagenesis of autolysis sites and generation of a stable mutant with retained kinetic properties. Biochemistry 33:9405鈥?413 CrossRef
  8. Prabu-Jeyabalan M, King NM, Nalivaika EA, Heilek-Snyder G, Cammack N, Schiffer CA (2006) Substrate envelope and drug resistance: crystal structure of RO1 in complex with wild-type human immunodeficiency virus type 1 protease. Antimicrob Agents Chemother 50:1518鈥?521 CrossRef
  9. Sanches M, Krauchenco S, Martins NH, Gustchina A, Wlodawer A, Polikarpov I (2007) Structural characterization of B and non-B subtypes of HIV-protease: insights into the natural susceptibility to drug resistance development. J Mol Biol 369:1029鈥?040 CrossRef
  10. Spinelli S, Liu QZ, Alzari PM, Hirel PH, Poljak RJ (1991) The three dimensional structure of the aspartyl protease from HIV-1 isolate BRU. Biochimie 73:1391鈥?396 CrossRef
  11. Velazquez-Campoy A, Vega S, Freire E (2002) Amplification of the effects of drug resistance mutations by background polymorphisms in HIV-1 protease from African subtypes. Biochemistry 41:8613鈥?619 CrossRef
  12. Weber IT, Agniswamy J (2009) HIV-1 protease: structural perspectives on drug resistance. Viruses 1:1110鈥?136 CrossRef
  
• 作者单位：Xi Huang (1)
  Ian Mitchelle S. de Vera (1)
  Angelo M. Veloro (1)
  James R. Rocca (2)
  Carlos Simmerling (3)
  Ben M. Dunn (4)
  Gail E. Fanucci (1)
  
  1. Department of Chemistry, University of Florida, PO Box 117200, Gainesville, FL, 32611, USA
  2. Advanced Magnetic Resonance and Imaging, McKnight Brain Institute, University of Florida, Gainesville, FL, 32610, USA
  3. Department of Chemistry, Stony Brook University, Stony Brook, NY, 11794, USA
  4. Department of Biochemistry and Molecular Biology, University of Florida, Gainesville, FL, 32610, USA
  
• ISSN：1874-270X

文摘

HIV-1 protease (HIV-1PR) is an essential drug target in the treatment of patients infected with HIV-1. Mutations are found to arise in over 38 of 99 amino acid sites in this protein in response to drug therapy or natural selection, where many are found combinations that alter enzyme kinetics or inhibitor susceptibility without a clear structural mechanism. In efforts to understand how these mutations alter the flexibility and dynamics of HIV-1PR, we report the backbone 1H, 13C, and 15N chemical shift assignments for subtypes C, circulating recombinant form CRF01_AE and a multi-drug resistant variant MDR 769. These assignments are essential for future work aimed at characterizing backbone dynamics, exchange dynamics and dynamics of protein/substrate or protein/inhibitor interactions.