Joint X-ray/Neutron Crystallographic Study of HIV-1 Protease with Clinical Inhibitor Amprenavir: Insights for Drug Design

被引：55

作者：

Weber, Irene T. ^{[1
,2
]}

Waltman, Mary Jo ^{[3
]}

Mustyakimov, Marat ^{[8
]}

Blakeley, Matthew P. ^{[4
]}

Keen, David A. ^{[5
]}

Ghosh, Arun K. ^{[6
,7
]}

Langan, Paul ^{[8
]}

Kovalevsky, Andrey Y. ^{[8
]}

机构：

[1] Georgia State Univ, Dept Chem, Atlanta, GA 30303 USA

[2] Georgia State Univ, Dept Biol, Atlanta, GA 30303 USA

[3] Los Alamos Natl Lab, Biosci Div, Los Alamos, NM 87545 USA

[4] Inst Max Von Laue Paul Langevin, Grenoble 9, France

[5] Rutherford Appleton Lab, ISIS Facil, Didcot OX11 0QX, Oxon, England

[6] Purdue Univ, Dept Chem, W Lafayette, IN 47907 USA

[7] Purdue Univ, Dept Med Chem, W Lafayette, IN 47907 USA

[8] Oak Ridge Natl Lab, Biol & Soft Matter Div, Oak Ridge, TN USA

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2013年 / 56卷 / 13期

关键词：

NEUTRON MACROMOLECULAR CRYSTALLOGRAPHY; RESOLUTION CRYSTAL-STRUCTURES; RESISTANT MUTANTS; IONIZATION STATES; ALDOSE REDUCTASE; HYDROGEN; COMPLEX; RAY; POTENT; GENERATION;

D O I：

10.1021/jm400684f

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

HIV-1 protease is an important target for the development of antiviral inhibitors to treat AIDS. A room-temperature joint X-ray/neutron structure of the protease in complex with clinical drug amprenavir has been determined at 2.0 angstrom resolution. The structure provides direct determination of hydrogen en atom positions in enzyme active enzyme-drug interactions suggests that some hydrogen bond's may be weaker than deduced from the non-hydrogen interatomic distances. This information may be valuable for the design of improved protease inhibitors.

引用

页码：5631 / 5635

页数：5

共 39 条

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