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标题：Protein conformational dynamics in the mechanism of HIV-1 protease catalysis
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作者：Vladimir Yu. Torbeev ; H. Raghuraman ; Donald Hamelberg 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2011
卷号：108
期号：52
页码：20982-20987
DOI：10.1073/pnas.1111202108
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：We have used chemical protein synthesis and advanced physical methods to probe dynamics-function correlations for the HIV-1 protease, an enzyme that has received considerable attention as a target for the treatment of AIDS. Chemical synthesis was used to prepare a series of unique analogues of the HIV-1 protease in which the flexibility of the "flap" structures (residues 37-61 in each monomer of the homodimeric protein molecule) was systematically varied. These analogue enzymes were further studied by X-ray crystallography, NMR relaxation, and pulse-EPR methods, in conjunction with molecular dynamics simulations. We show that conformational isomerization in the flaps is correlated with structural reorganization of residues in the active site, and that it is preorganization of the active site that is a rate-limiting factor in catalysis.
关键词：enzyme catalysis ; HIV protease ; protein dynamics ; protein NMR