X-ray crystallographic structure of ABT-378 (lopinavir) bound to HIV-1 protease

被引：80

作者：

Stoll, V

Qin, WY

Stewart, KD

Jakob, C

Park, C

Walter, K

Simmer, RL

Helfrich, R

Bussiere, D

Kao, J

Kempf, D

Sham, HL

Norbeck, DW

机构：

[1] Abbott Labs, Dept Biol Struct, Abbott Pk, IL 60064 USA

[2] Abbott Labs, Dept Genom & Mol Biol, Abbott Pk, IL 60064 USA

[3] Abbott Labs, Dept Antiinfect Res, Abbott Pk, IL 60064 USA

[4] Abbott Labs, Dept Pharmaceut Discovery, Abbott Pk, IL 60064 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2002年 / 10卷 / 08期

关键词：

D O I：

10.1016/S0968-0896(02)00051-2

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The crystal structure of ABT-378 (lopinavir), bound to the active site of HIV-1 protease is described. A comparison with crystal structures or ritonavir, A-78791, and BILA-2450 shows some analogous features With previous reported compounds. A cyclic urea unit in the P-2 position of ABT-378 is novel and makes two bidentate hydrogen bonds with Asp 29 of HIV-1 protease. In addition, a previously unreported shift in the Gly 48 carbonyl position is observed. A discussion of the structural features responsible for its high potency against wild-type HIV protease is given along with an analysis of the effect of active Site Mutations on potency in in vitro assays. (C) 2002 Elsevier Science Ltd. All rights reserved.

引用

页码：2803 / 2806

页数：4

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