2bx3

Publication Abstract from PubMed

The SARS coronavirus main proteinase (M(pro)) is a key enzyme in the processing of the viral polyproteins and thus an attractive target for the discovery of drugs directed against SARS. The enzyme has been shown by X-ray crystallography to undergo significant pH-dependent conformational changes. Here, we assess the conformational flexibility of the M(pro) by analysis of multiple crystal structures (including two new crystal forms) and by molecular dynamics (MD) calculations. The MD simulations take into account the different protonation states of two histidine residues in the substrate-binding site and explain the pH-activity profile of the enzyme. The low enzymatic activity of the M(pro) monomer and the need for dimerization are also discussed.

pH-dependent conformational flexibility of the SARS-CoV main proteinase (M(pro)) dimer: molecular dynamics simulations and multiple X-ray structure analyses.,Tan J, Verschueren KH, Anand K, Shen J, Yang M, Xu Y, Rao Z, Bigalke J, Heisen B, Mesters JR, Chen K, Shen X, Jiang H, Hilgenfeld R J Mol Biol. 2005 Nov 18;354(1):25-40. Epub 2005 Sep 23. PMID:16242152^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.