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1mn9

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{{STRUCTURE_1mn9| PDB=1mn9 | SCENE= }}
{{STRUCTURE_1mn9| PDB=1mn9 | SCENE= }}
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'''NDP kinase mutant (H122G) complex with RTP'''
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===NDP kinase mutant (H122G) complex with RTP===
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==Overview==
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Ribavirin used in therapies against hepatitis C virus (HCV) is potentially efficient against other viruses but presents a high cytotoxicity. Several ribavirin triphosphate analogs modified on the ribose moiety were synthesized and tested in vitro on the RNA polymerases of HCV, phage T7, and HIV-1 reverse transcriptase. Modified nucleotides with 2'-deoxy, 3'-deoxy, 2',3'-dideoxy, 2',3'-dideoxy-2',3'-dehydro, and 2',3'-epoxy-ribose inhibited the HCV enzyme but not the other two polymerases. They were also analyzed as substrates for nucleoside diphosphate (NDP) kinase, the enzyme responsible for the last step of the cellular activation of antiviral nucleoside analogs. An X-ray structure of NDP kinase complexed with ribavirin triphosphate was determined. It demonstrates that the analog binds as a normal substrate despite the modified base and confirms the crucial role of the 3'-hydroxyl group in the phosphorylation reaction. The 3'-hydroxyl is required for inhibition of the initiation step of RNA synthesis by HCV polymerase, and both sugar hydroxyls must be present to inhibit elongation. The 2'deoxyribavirin is the only derivative efficient in vitro against HCV polymerase and properly activated by NDP kinase.
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(as it appears on PubMed at http://www.pubmed.gov), where 12606760 is the PubMed ID number.
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{{ABSTRACT_PUBMED_12606760}}
==About this Structure==
==About this Structure==
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[[Category: Veron, M.]]
[[Category: Veron, M.]]
[[Category: Ndp kinase-ribavirin complex]]
[[Category: Ndp kinase-ribavirin complex]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 01:26:59 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Jul 3 00:27:10 2008''

Revision as of 21:27, 2 July 2008

Image:1mn9.png

Template:STRUCTURE 1mn9

NDP kinase mutant (H122G) complex with RTP

Template:ABSTRACT PUBMED 12606760

About this Structure

1MN9 is a Single protein structure of sequence from Dictyostelium discoideum. Full crystallographic information is available from OCA.

Reference

Structural analysis of the activation of ribavirin analogs by NDP kinase: comparison with other ribavirin targets., Gallois-Montbrun S, Chen Y, Dutartre H, Sophys M, Morera S, Guerreiro C, Schneider B, Mulard L, Janin J, Veron M, Deville-Bonne D, Canard B, Mol Pharmacol. 2003 Mar;63(3):538-46. PMID:12606760

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