1quv
CRYSTAL STRUCTURE OF THE RNA DIRECTED RNA POLYMERASE OF HEPATITIS C VIRUS
|
OverviewOverview
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.
About this StructureAbout this Structure
1QUV is a Single protein structure of sequence from Hepatitis c virus. Active as RNA-directed RNA polymerase, with EC number 2.7.7.48 Full crystallographic information is available from OCA.
ReferenceReference
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
Page seeded by OCA on Wed Nov 21 01:00:45 2007