| Literature DB >> 12057670 |
Vincent Stoll1, Wenying Qin, Kent D Stewart, Clarissa Jakob, Chang Park, K Walter, R L Simmer, Rosalind Helfrich, Dirk Bussiere, J Kao, Dale Kempf, Hing L Sham, Daniel W Norbeck.
Abstract
The crystal structure of ABT-378 (lopinavir), bound to the active site of HIV-1 protease is described. A comparison with crystal structures of 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.Entities:
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Year: 2002 PMID： 12057670 DOI： 10.1016/s0968-0896(02)00051-2
Source DB: PubMed Journal: Bioorg Med Chem ISSN： 0968-0896 Impact factor: 3.641