1c70 | pdb_00001c70

ALTERNATE BINDING SITE FOR THE P1-P3 GROUP OF A CLASS OF POTENT HIV-1 PROTEASE INHIBITORS AS A RESULT OF CONCERTED STRUCTURAL CHANGE IN 80'S LOOP.

spinqualitylabelsall models 1c70, resolution 2.50Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 1c70 is a 2 chain structure with sequence from Human immunodeficiency virus 1. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.5Å Ligands: L75 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function O92103_9HIV1 Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed Structures of the complexes of HIV protease inhibitor L--756,423 with the HIV-1 wild-type protease and of the inhibitors Indinavir, L-739,622 and Saquinavir with the mutant protease (9X) containing nine point mutations (Leu10Val, Lys20Met, Leu24Ile, Ser37Asp, Met46Ile, Ile54Val, Leu63Pro, Ala71Val, Val82Thr) have been determined. Comparative analysis of these structures reveals an alternate binding pocket for the P1-P3 group of Indinavir and L--756, 423. The alternate binding pocket is a result of concerted structural change in the 80s loop (residues 79-82) of the protease. The 80s loop is pulled away from the active site in order to accommodate the P1-P3 group, which is sandwiched between the flap and the 80s loop. This structural change is observed for the complexes of the wild type as well as the 9X mutant protease. The study reveals that the 80s loop is an intrinsically flexible loop in the wild-type HIV-1 protease and that mutations in this loop are not necessary to result in conformational changes. Conformation of this loop in the complex depends primarily upon the nature of the bound inhibitor and may be influenced by mutations in the protease. The results underscore the need to understand the intrinsic structural plasticity of the protease for the design of effective inhibitors against the wild-type and drug-resistant enzyme forms. In addition, the alternate binding pocket for the P1-P3 group of Indinavir and L--756,423 may be exploited for the design of potent inhibitors. An alternate binding site for the P1-P3 group of a class of potent HIV-1 protease inhibitors as a result of concerted structural change in the 80s loop of the protease.,Munshi S, Chen Z, Yan Y, Li Y, Olsen DB, Schock HB, Galvin BB, Dorsey B, Kuo LC Acta Crystallogr D Biol Crystallogr. 2000 Apr;56(Pt 4):381-8. PMID:10739910 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Immunodeficiency virus protease 3D structures

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