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Joint X-ray/neutron crystallographic study of HIV-1 protease with clinical inhibitor amprenavir: insights for drug design.

ABSTRACT: 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 Å resolution. The structure provides direct determination of hydrogen atom positions in the enzyme active site. Analysis of the enzyme-drug interactions suggests that some hydrogen bonds may be weaker than deduced from the non-hydrogen interatomic distances. This information may be valuable for the design of improved protease inhibitors.

SUBMITTER: Weber IT

PROVIDER: S-EPMC3815997 | biostudies-literature | 2013 Jul

REPOSITORIES: biostudies-literature

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Joint X-ray/neutron crystallographic study of HIV-1 protease with clinical inhibitor amprenavir: insights for drug design.

Weber Irene T IT Waltman Mary Jo MJ Mustyakimov Marat M Blakeley Matthew P MP Keen David A DA Ghosh Arun K AK Langan Paul P Kovalevsky Andrey Y AY

Journal of medicinal chemistry 20130628 13

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 Å resolution. The structure provides direct determination of hydrogen atom positions in the enzyme active site. Analysis of the enzyme-drug interactions suggests that some hydrogen bonds may be weaker than deduced from the non-hydrogen interatomic distances. This inform ...[more]

PMID: 23772563

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