1zsr
From Proteopedia
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|PDB= 1zsr |SIZE=350|CAPTION= <scene name='initialview01'>1zsr</scene>, resolution 2.06Å | |PDB= 1zsr |SIZE=350|CAPTION= <scene name='initialview01'>1zsr</scene>, resolution 2.06Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= <scene name='pdbligand=NH2:AMINO GROUP'>NH2</scene> | + | |LIGAND= <scene name='pdbligand=BOC:TERT-BUTYL+HYDROGEN+CARBONATE'>BOC</scene>, <scene name='pdbligand=CSO:S-HYDROXYCYSTEINE'>CSO</scene>, <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene>, <scene name='pdbligand=PS0:3(S)-AMINO-4-PHENYL-BUTAN-2(S)-OL'>PS0</scene> |
| - | |ACTIVITY= [http://en.wikipedia.org/wiki/HIV-1_retropepsin HIV-1 retropepsin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.23.16 3.4.23.16] | + | |ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/HIV-1_retropepsin HIV-1 retropepsin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.23.16 3.4.23.16] </span> |
|GENE= | |GENE= | ||
| + | |DOMAIN=<span class='plainlinks'>[http://www.ncbi.nlm.nih.gov/Structure/cdd/cddsrv.cgi?uid=pfam00077 RVP]</span> | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1zsr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1zsr OCA], [http://www.ebi.ac.uk/pdbsum/1zsr PDBsum], [http://www.fli-leibniz.de/cgi-bin/ImgLib.pl?CODE=1kfv JenaLib], [http://www.rcsb.org/pdb/explore.do?structureId=1zsr RCSB]</span> | ||
}} | }} | ||
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[[Category: Petrokova, H.]] | [[Category: Petrokova, H.]] | ||
[[Category: Skalova, T.]] | [[Category: Skalova, T.]] | ||
| - | [[Category: | + | [[Category: hiv]] |
| - | [[Category: | + | [[Category: inhibitor]] |
| + | [[Category: peptidomimetic]] | ||
| + | [[Category: protease]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Mar 26 06:18:42 2008'' |
Revision as of 04:18, 26 March 2008
| |||||||
| , resolution 2.06Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , , , | ||||||
| Activity: | HIV-1 retropepsin, with EC number 3.4.23.16 | ||||||
| Domains: | RVP | ||||||
| Resources: | FirstGlance, OCA, PDBsum, JenaLib, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
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-NH2
Overview
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.
About this Structure
1ZSR is a Single protein structure of sequence from Human immunodeficiency virus 1. Full crystallographic information is available from OCA.
Reference
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
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