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| {{STRUCTURE_1quv| PDB=1quv | SCENE= }} | | {{STRUCTURE_1quv| PDB=1quv | SCENE= }} |
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- | '''CRYSTAL STRUCTURE OF THE RNA DIRECTED RNA POLYMERASE OF HEPATITIS C VIRUS'''
| + | ===CRYSTAL STRUCTURE OF THE RNA DIRECTED RNA POLYMERASE OF HEPATITIS C VIRUS=== |
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- | ==Overview==
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- | BACKGROUND: Hepatitis C virus (HCV) is the major etiological agent of hepatocellular carcinoma, and HCV RNA-dependent RNA polymerase (RdRp) is one of the main potential targets for anti-HCV agents. HCV RdRp performs run-off copying replication in an RNA-selective manner for the template-primer duplex and the substrate, but the structural basis of this reaction mechanism has still to be elucidated. RESULTS: The three-dimensional structure of HCV RdRp was determined by X-ray crystallography at 2.5 A resolution. The compact HCV RdRp structure resembles a right hand, but has more complicated fingers and thumb domains than those of the other known polymerases, with a novel alpha-helix-rich subdomain (alpha fingers) as an addition to the fingers domain. The other fingers subdomain (beta fingers) is folded in the same manner as the fingers domain of human immunodeficiency virus (HIV) reverse transcriptase (RT), another RNA-dependent polymerase. The ribose-recognition site of HCV RdRp is constructed of hydrophilic residues, unlike those of DNA polymerases. The C-terminal region of HCV RdRp occupies the putative RNA-duplex-binding cleft. CONCLUSIONS: The structural basis of the RNA selectivity of HCV RdRp was elucidated from its crystal structure. The putative substrate-binding site with a shallow hydrophilic cavity should have ribonucleoside triphosphate (rNTP) as the preferred substrate. We propose that the unique alpha fingers might represent a common structural discriminator of the template-primer duplex that distinguishes between RNA and DNA during the replication of positive single-stranded RNA by viral RdRps. The C-terminal region might exert a regulatory function on the initiation and activity of HCV RdRp.
| + | The line below this paragraph, {{ABSTRACT_PUBMED_10574802}}, adds the Publication Abstract to the page |
| + | (as it appears on PubMed at http://www.pubmed.gov), where 10574802 is the PubMed ID number. |
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| ==About this Structure== | | ==About this Structure== |
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| [[Category: Replicase]] | | [[Category: Replicase]] |
| [[Category: Rna dependent rna polymerase]] | | [[Category: Rna dependent rna polymerase]] |
- | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 06:43:59 2008'' | + | |
| + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Jul 27 23:01:08 2008'' |
Revision as of 20:01, 27 July 2008
Template:STRUCTURE 1quv
CRYSTAL STRUCTURE OF THE RNA DIRECTED RNA POLYMERASE OF HEPATITIS C VIRUS
Template:ABSTRACT PUBMED 10574802
About this Structure
1QUV is a Single protein structure of sequence from Hepatitis c virus. Full crystallographic information is available from OCA.
Reference
Crystal structure of the RNA-dependent RNA polymerase of hepatitis C virus., Ago H, Adachi T, Yoshida A, Yamamoto M, Habuka N, Yatsunami K, Miyano M, Structure. 1999 Nov 15;7(11):1417-26. PMID:10574802
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