2ijd

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2ijd, resolution 3.40Å

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Crystal Structure of the Poliovirus Precursor Protein 3CD

Overview

Poliovirus 3CD is a multifunctional protein that serves as a precursor to, the protease 3C(pro) and the viral polymerase 3D(pol), and also plays a, role in the control of viral replication. Although 3CD is a fully, functional protease, it lacks polymerase activity. We have solved the, crystal structure of 3CD at 3.4-A resolution and the G64S fidelity mutant, of 3D(pol) at 3.0-A resolution. In the 3CD structure, the 3C and 3D, domains are joined by a poorly-ordered polypeptide linker, possibly to, facilitate its cleavage, in an arrangement that precludes intramolecular, proteolysis. The polymerase active site is intact in both the 3CD and G64S, 3D(pol) structures, despite the disruption of a network proposed to, position key residues in the active site. Therefore, changes in molecular, flexibility may be responsible for the differences in fidelity and, polymerase activity. Extensive packing contacts between symmetry-related, 3CD molecules and the approach of the 3C domain's N-terminus to the VPg, binding site suggest how 3D(pol) makes biologically relevant interactions, with proteins 3C, 3CD, and 3BCD that control the uridylylation of VPg, during the initiation of viral replication. Indeed, mutations designed to, disrupt these interfaces have pronounced effects on the uridylylation, reaction in vitro.

About this Structure

2IJD is a Single protein structure of sequence from Human poliovirus 1 with and as ligands. Full crystallographic information is available from OCA.

Reference

Crystal structure of poliovirus 3CD: virally-encoded protease and precursor to the RNA-dependent RNA polymerase., Marcotte LL, Wass AB, Gohara DW, Pathak HB, Arnold JJ, Filman DJ, Cameron CE, Hogle JM, J Virol. 2007 Jan 24;. PMID:17251299

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