1bdr
From Proteopedia
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HIV-1 (2: 31, 33-37) PROTEASE COMPLEXED WITH INHIBITOR SB203386
Overview
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.
About this Structure
1BDR is a Single protein structure of sequence from Human immunodeficiency virus 1 with IM1 as ligand. Active as HIV-1 retropepsin, with EC number 3.4.23.16 Structure known Active Site: IM1. Full crystallographic information is available from OCA.
Reference
Structural role of the 30's loop in determining the ligand specificity of the human immunodeficiency virus protease., Swairjo MA, Towler EM, Debouck C, Abdel-Meguid SS, Biochemistry. 1998 Aug 4;37(31):10928-36. PMID:9692985
Page seeded by OCA on Mon Nov 5 15:53:58 2007
