1TCW

SIV PROTEASE COMPLEXED WITH INHIBITOR SB203386

1TCW の概要

• エントリーDOI: 10.2210/pdb1tcw/pdb
• 分子名称: SIV PROTEASE, (2R,4S,5S,1'S)-2-PHENYLMETHYL-4-HYDROXY-5-(TERT-BUTOXYCARBONYL)AMINO-6-PHENYL HEXANOYL-N-(1'-IMIDAZO-2-YL)-2'-METHYLPROPANAMIDE (3 entities in total)
• 機能のキーワード: aids, polyprotein, hydrolase, aspartyl protease, endonuclease, rna-directed dna polymerase, acid protease, hydrolase (acid protease)
• 由来する生物種: Simian immunodeficiency virus
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 22520.28

構造登録者

Hoog, S.S.,Abdel-Meguid, S.S. (登録日: 1996-06-05, 公開日: 1996-12-07, 最終更新日: 2024-02-14)

主引用文献

Hoog, S.S.,Towler, E.M.,Zhao, B.,Doyle, M.L.,Debouck, C.,Abdel-Meguid, S.S.
Human immunodeficiency virus protease ligand specificity conferred by residues outside of the active site cavity.
Biochemistry, 35:10279-10286, 1996

PubMed Abstract: To gain greater understanding of the structural basis of human immunodeficiency virus (HIV) protease ligand specificity, we have crystallized and determined the structures of the HIV-1 protease (Val32Ile, Ile47Val, Val82Ile) triple mutant and simian immunodeficiency virus (SIV) protease in complex with SB203386, a tripeptide analogue inhibitor containing a C-terminal imidazole substituent as an amide bond isostere. SB203386 is a potent inhibitor of HIV-1 protease (Ki = 18 nM) but shows decreased inhibition of the HIV-1 protease (Val32Ile, Ile47Val, Val82Ile) triple mutant (Ki = 112 nM) and SIV protease (Ki = 960 nM). Although SB203386 binds in the active site cavity of the triple mutant in a similar fashion to its binding to the wild-type HIV-1 protease [Abdel-Meguid et al. (1994) Biochemistry 33, 11671], it binds to SIV protease in an unexpected mode showing two inhibitor molecules each binding to half of the active site. Comparison of these two structures and that of the wild-type HIV-1 protease bound to SB203386 reveals that HIV protease ligand specificity is imparted by residues outside of the catalytic pocket, which causes subtle changes in its shape. Furthermore, this work illustrates the importance of structural studies in order to understand the structure-activity relationship (SAR) between related enzymes.

PubMed: 8756683
DOI: 10.1021/bi960179j

実験手法

X-RAY DIFFRACTION (2.4 Å)