1csj

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1csj, resolution 2.8Å

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CRYSTAL STRUCTURE OF THE RNA-DEPENDENT RNA POLYMERASE OF HEPATITIS C VIRUS

Overview

We report the crystal structure of the RNA-dependent RNA polymerase of, hepatitis C virus, a major human pathogen, to 2.8-A resolution. This, enzyme is a key target for developing specific antiviral therapy. The, structure of the catalytic domain contains 531 residues folded in the, characteristic fingers, palm, and thumb subdomains. The fingers subdomain, contains a region, the "fingertips," that shares the same fold with, reverse transcriptases. Superposition to the available structures of the, latter shows that residues from the palm and fingertips are structurally, equivalent. In addition, it shows that the hepatitis C virus polymerase, was crystallized in a closed fingers conformation, similar to HIV-1, reverse transcriptase in ternary complex with DNA and dTTP [Huang H., Chopra, R., Verdine, G. L. & Harrison, S. C. (1998) Science 282, 1669-1675]. This superposition reveals the majority of the amino acid, residues of the hepatitis C virus enzyme that are likely to be implicated, in binding to the replicating RNA molecule and to the incoming NTP. It, also suggests a rearrangement of the thumb domain as well as a possible, concerted movement of thumb and fingertips during translocation of the RNA, template-primer in successive polymerization rounds.

About this Structure

1CSJ 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.

Reference

Crystal structure of the RNA-dependent RNA polymerase of hepatitis C virus., Bressanelli S, Tomei L, Roussel A, Incitti I, Vitale RL, Mathieu M, De Francesco R, Rey FA, Proc Natl Acad Sci U S A. 1999 Nov 9;96(23):13034-9. PMID:10557268

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