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

Irene T. Weber; Mary Jo Waltman; Marat Mustyakimov; Matthew P. Blakeley; David A. Keen; Arun K. Ghosh; Paul Langan; Andrey Y. Kovalevsky

doi:10.1021/jm400684f

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

Irene T. Weber
, Mary Jo Waltman
, Marat Mustyakimov
, Matthew P. Blakeley
, David A. Keen
, Arun K. Ghosh
, Paul Langan
, Andrey Y. Kovalevsky

Research output: Contribution to journal › Article › peer-review

59 Scopus citations

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.

Original language	English
Pages (from-to)	5631-5635
Number of pages	5
Journal	Journal of Medicinal Chemistry
Volume	56
Issue number	13
DOIs	https://doi.org/10.1021/jm400684f
State	Published - Jul 11 2013

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title = "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 {\AA} 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.",

author = "Weber, \{Irene T.\} and Waltman, \{Mary Jo\} and Marat Mustyakimov and Blakeley, \{Matthew P.\} and Keen, \{David A.\} and Ghosh, \{Arun K.\} and Paul Langan and Kovalevsky, \{Andrey Y.\}",

year = "2013",

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doi = "10.1021/jm400684f",

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T1 - Joint X-ray/neutron crystallographic study of HIV-1 protease with clinical inhibitor amprenavir

T2 - Insights for drug design

AU - Weber, Irene T.

AU - Waltman, Mary Jo

AU - Mustyakimov, Marat

AU - Blakeley, Matthew P.

AU - Keen, David A.

AU - Ghosh, Arun K.

AU - Langan, Paul

AU - Kovalevsky, Andrey Y.

PY - 2013/7/11

Y1 - 2013/7/11

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/84880148483

U2 - 10.1021/jm400684f

DO - 10.1021/jm400684f

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JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

IS - 13

ER -

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

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