2PSV

Crystal Structure of wild type HIV-1 protease in complex with CARB-KB45

2PSV の概要

• エントリーDOI: 10.2210/pdb2psv/pdb
• 関連するPDBエントリー: 2psu
• 分子名称: Protease, PHOSPHATE ION, ACETATE ION, ... (5 entities in total)
• 機能のキーワード: drug design, hiv-1 protease, protease inhibitors, hydrolase
• 由来する生物種: Human immunodeficiency virus 1
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 22453.11

構造登録者

Schiffer, C.A.,Nalam, M.N.L. (登録日: 2007-05-07, 公開日: 2007-06-05, 最終更新日: 2023-08-30)

主引用文献

Chellappan, S.,Kiran Kumar Reddy, G.S.,Ali, A.,Nalam, M.N.,Anjum, S.G.,Cao, H.,Kairys, V.,Fernandes, M.X.,Altman, M.D.,Tidor, B.,Rana, T.M.,Schiffer, C.A.,Gilson, M.K.
Design of Mutation-resistant HIV Protease Inhibitors with the Substrate Envelope Hypothesis.
Chem.Biol.Drug Des., 69:298-313, 2007

PubMed Abstract: There is a clinical need for HIV protease inhibitors that can evade resistance mutations. One possible approach to designing such inhibitors relies upon the crystallographic observation that the substrates of HIV protease occupy a rather constant region within the binding site. In particular, it has been hypothesized that inhibitors which lie within this region will tend to resist clinically relevant mutations. The present study offers the first prospective evaluation of this hypothesis, via computational design of inhibitors predicted to conform to the substrate envelope, followed by synthesis and evaluation against wild-type and mutant proteases, as well as structural studies of complexes of the designed inhibitors with HIV protease. The results support the utility of the substrate envelope hypothesis as a guide to the design of robust protease inhibitors.

PubMed: 17539822
DOI: 10.1111/j.1747-0285.2007.00514.x

実験手法

X-RAY DIFFRACTION (1.75 Å)