2oin
From Proteopedia
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|PDB= 2oin |SIZE=350|CAPTION= <scene name='initialview01'>2oin</scene>, resolution 2.500Å | |PDB= 2oin |SIZE=350|CAPTION= <scene name='initialview01'>2oin</scene>, resolution 2.500Å | ||
|SITE= | |SITE= | ||
- | |LIGAND= <scene name='pdbligand=ZN:ZINC ION'>ZN</scene> | + | |LIGAND= <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene> |
|ACTIVITY= | |ACTIVITY= | ||
- | |GENE= NS3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id= Hepatitis C virus]) | + | |GENE= NS3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=11103 Hepatitis C virus]) |
+ | |DOMAIN= | ||
+ | |RELATEDENTRY= | ||
+ | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2oin FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2oin OCA], [http://www.ebi.ac.uk/pdbsum/2oin PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2oin RCSB]</span> | ||
}} | }} | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Wei, Y.]] | [[Category: Wei, Y.]] | ||
- | [[Category: ZN]] | ||
[[Category: crystal structure]] | [[Category: crystal structure]] | ||
[[Category: hcv]] | [[Category: hcv]] | ||
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[[Category: r155k mutant]] | [[Category: r155k mutant]] | ||
- | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 04:18:24 2008'' |
Revision as of 01:18, 31 March 2008
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, resolution 2.500Å | |||||||
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Ligands: | |||||||
Gene: | NS3 (Hepatitis C virus) | ||||||
Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
Coordinates: | save as pdb, mmCIF, xml |
crystal structure of HCV NS3-4A R155K muntant
Overview
Telaprevir (VX-950) is a highly selective, potent inhibitor of the hepatitis C virus (HCV) NS3.4A serine protease. It has demonstrated strong antiviral activity in patients chronically infected with genotype 1 HCV when dosed alone or in combination with peginterferon alfa-2a. Substitutions of Arg(155) of the HCV NS3 protease domain have been previously detected in HCV isolates from some patients during telaprevir dosing. In this study, Arg(155) was replaced with various residues in genotype 1a protease domain proteins and in genotype 1b HCV subgenomic replicons. Characterization of both the purified enzymes and reconstituted replicon cells demonstrated that substitutions of Arg(155) with these residues conferred low level resistance to telaprevir (<25-fold). An x-ray structure of genotype 1a HCV protease domain with the R155K mutation, in a complex with an NS4A co-factor peptide, was determined at a resolution of 2.5A. The crystal structure of the R155K protease is essentially identical to that of the wild-type apoenzyme (Protein Data Bank code 1A1R) except for the side chain of mutated residue 155. Telaprevir was docked into the x-ray structure of the R155K protease, and modeling analysis suggests that the P2 group of telaprevir loses several hydrophobic contacts with the Lys(155) side chain. It was demonstrated that replicon cells containing substitutions at NS3 protease residue 155 remain fully sensitive to interferon alpha or ribavirin. Finally, these variant replicons were shown to have reduced replication capacity compared with the wild-type HCV replicon in cells.
About this Structure
2OIN is a Single protein structure of sequence from Hepatitis c virus. Full crystallographic information is available from OCA.
Reference
Phenotypic and structural analyses of hepatitis C virus NS3 protease Arg155 variants: sensitivity to telaprevir (VX-950) and interferon alpha., Zhou Y, Muh U, Hanzelka BL, Bartels DJ, Wei Y, Rao BG, Brennan DL, Tigges AM, Swenson L, Kwong AD, Lin C, J Biol Chem. 2007 Aug 3;282(31):22619-28. Epub 2007 Jun 6. PMID:17556358
Page seeded by OCA on Mon Mar 31 04:18:24 2008
Categories: Hepatitis c virus | Single protein | Wei, Y. | Crystal structure | Hcv | Hydrolase | Ns3-4a | Protease | R155k mutant