1BDR

HIV-1 (2: 31, 33-37) PROTEASE COMPLEXED WITH INHIBITOR SB203386

1BDR の概要

• エントリーDOI: 10.2210/pdb1bdr/pdb
• 分子名称: HIV-1 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: hydrolase, aids, polyprotein, aspartyl protease, acid protease, hydroxyethylene isostere inhibitor, substrate analogue inhibitor
• 由来する生物種: Human immunodeficiency virus 1
• 細胞内の位置: Matrix protein p17: Virion (Potential). Capsid protein p24: Virion (Potential). Nucleocapsid protein p7: Virion (Potential). Reverse transcriptase/ribonuclease H: Virion (Potential). Integrase: Virion (Potential): P04587
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 21873.90

構造登録者

Swairjo, M.A.,Abdel-Meguid, S.S. (登録日: 1998-05-10, 公開日: 1998-10-14, 最終更新日: 2024-05-22)

主引用文献

Swairjo, M.A.,Towler, E.M.,Debouck, C.,Abdel-Meguid, S.S.
Structural role of the 30's loop in determining the ligand specificity of the human immunodeficiency virus protease.
Biochemistry, 37:10928-10936, 1998

PubMed Abstract: The structural basis of ligand specificity in human immunodeficiency virus (HIV) protease has been investigated by determining the crystal structures of three chimeric HIV proteases complexed with SB203386, a tripeptide analogue inhibitor. The chimeras are constructed by substituting amino acid residues in the HIV type 1 (HIV-1) protease sequence with the corresponding residues from HIV type 2 (HIV-2) in the region spanning residues 31-37 and in the active site cavity. SB203386 is a potent inhibitor of HIV-1 protease (Ki = 18 nM) but has a decreased affinity for HIV-2 protease (Ki = 1280 nM). Crystallographic analysis reveals that substitution of residues 31-37 (30's loop) with those of HIV-2 protease renders the chimera similar to HIV-2 protease in both the inhibitor binding affinity and mode of binding (two inhibitor molecules per protease dimer). However, further substitution of active site residues 47 and 82 has a compensatory effect which restores the HIV-1-like inhibitor binding mode (one inhibitor molecule in the center of the protease active site) and partially restores the affinity. Comparison of the three chimeric protease structures with those of HIV-1 and SIV proteases complexed with the same inhibitor reveals structural changes in the flap regions and the 80's loops, as well as changes in the dimensions of the active site cavity. The study provides structural evidence of the role of the 30's loop in conferring inhibitor specificity in HIV proteases.

PubMed: 9692985
DOI: 10.1021/bi980784h

実験手法

X-RAY DIFFRACTION (2.8 Å)