1zsr

Crystal structure of wild type HIV-1 protease (BRU isolate) with a hydroxyethylamine peptidomimetic inhibitor BOC-PHE-PSI[S-CH(OH)CH2NH]-PHE-GLU-PHE-NH2Crystal structure of wild type HIV-1 protease (BRU isolate) with a hydroxyethylamine peptidomimetic inhibitor BOC-PHE-PSI[S-CH(OH)CH2NH]-PHE-GLU-PHE-NH2

Structural highlights 1zsr 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. Ligands: NonStd Res: Related: 1fqx, 1m0b, 1lzq, 1iiq, 1z8c, 1zbg, 1zj7, 1zlf, 1zpk, 1zsf Activity: HIV-1 retropepsin, with EC number 3.4.23.16 Resources: FirstGlance, OCA, RCSB, PDBsum 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 Peptidomimetic inhibitors of human immunodeficiency virus-1 protease are successful lead substances for the development of virostatic drugs against HIV as the causative agent of acquired immunodeficiency syndrome (AIDS). The hydroxyethylamine isostere of the proteolytic cleavage intermediate provides a suitable replacement for the peptide bond. A series of acyclic pseudopeptide inhibitors with the hydroxyethylamine isostere varying in chiral carbon configuration and P'2 residue type were structurally analysed by single-crystal X-ray crystallography. The compounds inhibit HIV protease with subnanomolar inhibition constants and block viral replication in tissue cultures. Here, the structure of such a complex with the R configuration of the isosteric group (PDB code 1zsf) is presented together with newly available synchrotron data for a complex with the S stereoisomer of the inhibitor (PDB code 1zsr). Comparison of the structure and binding with other complexes of HIV-1 protease and similar inhibitors contributes to the understanding of how these molecules bind to the wild-type form of this enzyme. The hydroxy group of the R stereoisomer interacts with one of the catalytic aspartic acids by a short hydrogen bond with rather extreme geometry. The change of configuration of the chiral carbon bearing the hydroxyl from S to R does not influence the inhibition efficiency in this case. On the role of the R configuration of the reaction-intermediate isostere in HIV-1 protease-inhibitor binding: X-ray structure at 2.0 A resolution.,Duskova J, Dohnalek J, Skalova T, Petrokova H, Vondrackova E, Hradilek M, Konvalinka J, Soucek M, Brynda J, Fabry M, Sedlacek J, Hasek J Acta Crystallogr D Biol Crystallogr. 2006 May;62(Pt 5):489-97. Epub 2006, Apr 19. PMID:16627941 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Virus protease

spinqualitylabelsall models 1zsr, resolution 2.06Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image