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- Title
Crystal structure of gingipain R: an Arg-specific bacterial cysteine proteinase with a caspase-like fold.
- Authors
Eichinger, A; Beisel, H G; Jacob, U; Huber, R; Medrano, F J; Banbula, A; Potempa, J; Travis, J; Bode, W
- Abstract
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.
- Publication
The EMBO journal, 1999, Vol 18, Issue 20, p5453
- ISSN
0261-4189
- Publication type
Journal Article
- DOI
10.1093/emboj/18.20.5453