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3MXE

Crystal structure of HIV-1 protease inhibitor, KC32 complexed with wild-type protease

Summary for 3MXE
Entry DOI10.2210/pdb3mxe/pdb
Related3MXD
DescriptorHIV-1 protease, (5S)-N-{(1S,2R)-3-[(1,3-benzothiazol-6-ylsulfonyl)(2-methylpropyl)amino]-1-benzyl-2-hydroxypropyl}-2-oxo-3-[2-(trifluoromethyl)phenyl]-1,3-oxazolidine-5-carboxamide, PHOSPHATE ION, ... (5 entities in total)
Functional Keywordsdrug design, protease inhibitors, hiv protease, hydrolase, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
Biological sourceHIV-1 M:B_ARV2/SF2 (HIV-1)
Cellular locationGag-Pol polyprotein: Host cell membrane; Lipid-anchor. Matrix protein p17: Virion membrane; Lipid- anchor . Capsid protein p24: Virion . Nucleocapsid protein p7: Virion . Reverse transcriptase/ribonuclease H: Virion . Integrase: Virion : P03369
Total number of polymer chains2
Total formula weight22476.35
Authors
Nalam, M.N.L.,Schiffer, C.A. (deposition date: 2010-05-07, release date: 2010-11-10, Last modification date: 2024-03-13)
Primary citationAli, A.,Reddy, G.S.,Nalam, M.N.,Anjum, S.G.,Cao, H.,Schiffer, C.A.,Rana, T.M.
Structure-Based Design, Synthesis, and Structure-Activity Relationship Studies of HIV-1 Protease Inhibitors Incorporating Phenyloxazolidinones.
J.Med.Chem., 53:7699-7708, 2010
Cited by
PubMed Abstract: A series of new HIV-1 protease inhibitors with the hydroxyethylamine core and different phenyloxazolidinone P2 ligands were designed and synthesized. Variation of phenyl substitutions at the P2 and P2' moieties significantly affected the binding affinity and antiviral potency of the inhibitors. In general, compounds with 2- and 4-substituted phenyloxazolidinones at P2 exhibited lower binding affinities than 3-substituted analogues. Crystal structure analyses of ligand-enzyme complexes revealed different binding modes for 2- and 3-substituted P2 moieties in the protease S2 binding pocket, which may explain their different binding affinities. Several compounds with 3-substituted P2 moieties demonstrated picomolar binding affinity and low nanomolar antiviral potency against patient-derived viruses from HIV-1 clades A, B, and C, and most retained potency against drug-resistant viruses. Further optimization of these compounds using structure-based design may lead to the development of novel protease inhibitors with improved activity against drug-resistant strains of HIV-1.
PubMed: 20958050
DOI: 10.1021/jm1008743
PDB entries with the same primary citation
Experimental method
X-RAY DIFFRACTION (1.85 Å)
Structure validation

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