1mn9

NDP kinase mutant (H122G) complex with RTP

spinqualitylabelsall models 1mn9, resolution 2.90Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 1mn9 is a 3 chain structure with sequence from Atcc 11735. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: MG, RTP Related: 1f3f, 1nue Activity: Nucleoside-diphosphate kinase, with EC number 2.7.4.6 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed 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. 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Nucleoside diphosphate kinase 3D structures

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