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2q54
From Proteopedia
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[[Image:2q54.jpg|left|200px]] | [[Image:2q54.jpg|left|200px]] | ||
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'''Crystal structure of KB73 bound to HIV-1 protease''' | '''Crystal structure of KB73 bound to HIV-1 protease''' | ||
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[[Category: Nalam, M N.L.]] | [[Category: Nalam, M N.L.]] | ||
[[Category: Schiffer, C A.]] | [[Category: Schiffer, C A.]] | ||
| - | [[Category: | + | [[Category: Drug design]] |
| - | [[Category: | + | [[Category: Hiv-1 protease]] |
| - | [[Category: | + | [[Category: Hydrolase]] |
| - | [[Category: | + | [[Category: Protease inhibitor]] |
| - | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 14:22:31 2008'' | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | |
Revision as of 11:22, 4 May 2008
Crystal structure of KB73 bound to HIV-1 protease
Overview
A series of novel HIV-1 protease inhibitors based on two pseudosymmetric dipeptide isosteres have been synthesized and evaluated. The inhibitors were designed by incorporating N-phenyloxazolidinone-5-carboxamides into the hydroxyethylene and (hydroxyethyl)hydrazine dipeptide isosteres as P2 and P2' ligands. Compounds with (S)-phenyloxazolidinones attached at a position proximal to the central hydroxyl group showed low nM inhibitory activities against wild-type HIV-1 protease. Selected compounds were further evaluated for their inhibitory activities against a panel of multidrug-resistant protease variants and for their antiviral potencies in MT-4 cells. The crystal structures of lopinavir (LPV) and two new inhibitors containing phenyloxazolidinone-based ligands in complex with wild-type HIV-1 protease have been determined. A comparison of the inhibitor-protease structures with the LPV-protease structure provides valuable insight into the binding mode of the new inhibitors to the protease enzyme. Based on the crystal structures and knowledge of structure-activity relationships, new inhibitors can be designed with enhanced enzyme inhibitory and antiviral potencies.
About this Structure
2Q54 is a Single protein structure of sequence from Human immunodeficiency virus 1. Full crystallographic information is available from OCA.
Reference
Design and synthesis of HIV-1 protease inhibitors incorporating oxazolidinones as P2/P2' ligands in pseudosymmetric dipeptide isosteres., Reddy GS, Ali A, Nalam MN, Anjum SG, Cao H, Nathans RS, Schiffer CA, Rana TM, J Med Chem. 2007 Sep 6;50(18):4316-28. Epub 2007 Aug 16. PMID:17696512 Page seeded by OCA on Sun May 4 14:22:31 2008
