2ckw

From Proteopedia

---

Revision as of 07:02, 21 November 2007

proteopedia linkproteopedia link

spinqualitylabelsall models 2ckw, resolution 2.30Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

THE 2.3 A RESOLUTION STRUCTURE OF THE SAPPORO VIRUS RNA DEPENDANT RNA POLYMERASE.

Overview

Sapoviruses are one of the major agents of acute gastroenteritis in, childhood. They form a tight genetic cluster (genus) in the Caliciviridae, family that regroups both animal and human pathogenic strains. No, permissive tissue culture has been developed for human sapovirus, limiting, its characterization to surrogate systems. We report here on the first, extensive characterization of the key enzyme of replication, the, RNA-dependent RNA polymerase (RdRp) associated with the 3D(pol)-like, protein. Enzymatically active sapovirus 3D(pol) and its defective mutant, were expressed in Escherichia coli and purified. The overall structure of, the sapovirus 3D(pol) was determined by X-ray crystallography to 2.32-A, resolution. It revealed a right hand fold typical for template-dependent, polynucleotide polymerases. The carboxyl terminus is located within the, active site cleft, as observed in the RdRp of some (norovirus) but not, other (lagovirus) caliciviruses. Sapovirus 3D(pol) prefers Mn(2+) over, Mg(2+) but may utilize either as a cofactor in vitro. In a synthetic RNA, template-dependent reaction, sapovirus 3D(pol) synthesizes a, double-stranded RNA or labels the template 3' terminus by terminal, transferase activity. Initiation of RNA synthesis occurs de novo on, heteropolymeric templates or in a primer-dependent manner on, polyadenylated templates. Strikingly, this mode of initiation of RNA, synthesis was also described for norovirus, but not for lagovirus, suggesting structural and functional homologies in the RNA-dependent RNA, polymerase of human pathogenic caliciviruses. This first experimental, evidence makes sapovirus 3D(pol) an attractive target for developing drugs, to control calicivirus infection in humans.

About this Structure

2CKW is a Single protein structure of sequence from Sapporo virus. Active as RNA-directed RNA polymerase, with EC number 2.7.7.48 Full crystallographic information is available from OCA.

Reference

Structural and functional characterization of sapovirus RNA-dependent RNA polymerase., Fullerton SW, Blaschke M, Coutard B, Gebhardt J, Gorbalenya A, Canard B, Tucker PA, Rohayem J, J Virol. 2007 Feb;81(4):1858-71. Epub 2006 Nov 22. PMID:17121797

Page seeded by OCA on Wed Nov 21 09:09:24 2007