1quv: Difference between revisions
New page: left|200px<br /><applet load="1quv" size="450" color="white" frame="true" align="right" spinBox="true" caption="1quv, resolution 2.50Å" /> '''CRYSTAL STRUCTURE OF... |
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[[Image:1quv.jpg|left|200px]]<br /><applet load="1quv" size=" | [[Image:1quv.jpg|left|200px]]<br /><applet load="1quv" size="350" color="white" frame="true" align="right" spinBox="true" | ||
caption="1quv, resolution 2.50Å" /> | caption="1quv, resolution 2.50Å" /> | ||
'''CRYSTAL STRUCTURE OF THE RNA DIRECTED RNA POLYMERASE OF HEPATITIS C VIRUS'''<br /> | '''CRYSTAL STRUCTURE OF THE RNA DIRECTED RNA POLYMERASE OF HEPATITIS C VIRUS'''<br /> | ||
==Overview== | ==Overview== | ||
BACKGROUND: Hepatitis C virus (HCV) is the major etiological agent of | 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 Structure== | ==About this Structure== | ||
1QUV is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Hepatitis_c_virus Hepatitis c virus]. Active as [http://en.wikipedia.org/wiki/RNA-directed_RNA_polymerase RNA-directed RNA polymerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.48 2.7.7.48] Full crystallographic information is available from [http:// | 1QUV is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Hepatitis_c_virus Hepatitis c virus]. Active as [http://en.wikipedia.org/wiki/RNA-directed_RNA_polymerase RNA-directed RNA polymerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.48 2.7.7.48] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1QUV OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: rna dependent rna polymerase]] | [[Category: rna dependent rna polymerase]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:44:05 2008'' | ||
Revision as of 15:44, 21 February 2008
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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
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