1cvr: Difference between revisions

[[Image:1cvr.gif|left|200px]]<br /><applet load="1cvr" size="350" color="white" frame="true" align="right" spinBox="true"  

Gingipains are cysteine proteinases acting as key virulence factors of the bacterium Porphyromonas gingivalis, the major pathogen in periodontal disease. The 1.5 and 2.0 A crystal structures of free and D-Phe-Phe-Arg-chloromethylketone-inhibited gingipain R reveal a 435-residue, single-polypeptide chain organized into a catalytic and an immunoglobulin-like domain. The catalytic domain is subdivided into two subdomains comprising four- and six-stranded beta-sheets sandwiched by alpha-helices. Each subdomain bears topological similarities to the p20-p10 heterodimer of caspase-1. The second subdomain harbours the Cys-His catalytic diad and a nearby Glu arranged around the S1 specificity pocket, which carries an Asp residue to enforce preference for Arg-P1 residues. This gingipain R structure is an excellent template for the rational design of drugs with a potential to cure and prevent periodontitis. Here we show the binding mode of an arginine-containing inhibitor in the active-site, thus identifying major interaction sites defining a suitable pharmacophor.

1CVR is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Porphyromonas_gingivalis Porphyromonas gingivalis] with <scene name='pdbligand=CA:'>CA</scene> and <scene name='pdbligand=ZN:'>ZN</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Gingipain_R Gingipain R], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.22.37 3.4.22.37] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1CVR OCA].  

[[Category: Beisel, H G.]]

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