1mn9: Difference between revisions
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[[Image:1mn9.gif|left|200px]] | [[Image:1mn9.gif|left|200px]] | ||
'''NDP kinase mutant (H122G) complex with RTP''' | {{Structure | ||
|PDB= 1mn9 |SIZE=350|CAPTION= <scene name='initialview01'>1mn9</scene>, resolution 2.9Å | |||
|SITE= | |||
|LIGAND= <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene> and <scene name='pdbligand=RTP:RIBAVIRIN TRIPHOSPHATE'>RTP</scene> | |||
|ACTIVITY= [http://en.wikipedia.org/wiki/Nucleoside-diphosphate_kinase Nucleoside-diphosphate kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.4.6 2.7.4.6] | |||
|GENE= | |||
}} | |||
'''NDP kinase mutant (H122G) complex with RTP''' | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
1MN9 is a [ | 1MN9 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Dictyostelium_discoideum Dictyostelium discoideum]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1MN9 OCA]. | ||
==Reference== | ==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:[http:// | 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:[http://www.ncbi.nlm.nih.gov/pubmed/12606760 12606760] | ||
[[Category: Dictyostelium discoideum]] | [[Category: Dictyostelium discoideum]] | ||
[[Category: Nucleoside-diphosphate kinase]] | [[Category: Nucleoside-diphosphate kinase]] | ||
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[[Category: ndp kinase-ribavirin complex]] | [[Category: ndp kinase-ribavirin complex]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 12:45:35 2008'' | ||
Revision as of 13:45, 20 March 2008
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| , resolution 2.9Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | and | ||||||
| Activity: | Nucleoside-diphosphate kinase, with EC number 2.7.4.6 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
NDP kinase mutant (H122G) complex with RTP
OverviewOverview
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.
About this StructureAbout this Structure
1MN9 is a Single protein structure of sequence from Dictyostelium discoideum. Full crystallographic information is available from OCA.
ReferenceReference
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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