This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.

Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.


2oin

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Line 1: Line 1:
-
[[Image:2oin.jpg|left|200px]]
+
{{Seed}}
 +
[[Image:2oin.png|left|200px]]
<!--
<!--
Line 9: Line 10:
{{STRUCTURE_2oin| PDB=2oin | SCENE= }}
{{STRUCTURE_2oin| PDB=2oin | SCENE= }}
-
'''crystal structure of HCV NS3-4A R155K muntant'''
+
===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 (&lt;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.
+
The line below this paragraph, {{ABSTRACT_PUBMED_17556358}}, adds the Publication Abstract to the page
 +
(as it appears on PubMed at http://www.pubmed.gov), where 17556358 is the PubMed ID number.
 +
-->
 +
{{ABSTRACT_PUBMED_17556358}}
==About this Structure==
==About this Structure==
Line 29: Line 33:
[[Category: Protease]]
[[Category: Protease]]
[[Category: R155k mutant]]
[[Category: R155k mutant]]
-
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 11:00:02 2008''
+
 
 +
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 18:46:21 2008''

Revision as of 15:46, 28 July 2008

Image:2oin.png

Template:STRUCTURE 2oin

crystal structure of HCV NS3-4A R155K muntant

Template:ABSTRACT PUBMED 17556358

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 Jul 28 18:46:21 2008

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2oin"
Personal tools