1CVR

Crystal structure of the Arg specific cysteine proteinase gingipain R (RGPB)

Summary for 1CVR

• Entry DOI: 10.2210/pdb1cvr/pdb
• Related PRD ID: PRD_001160
• Descriptor: GINGIPAIN R, D-phenylalanyl-N-[(3S)-6-carbamimidamido-1-chloro-2-oxohexan-3-yl]-L-phenylalaninamide, CALCIUM ION, ... (5 entities in total)
• Functional Keywords: caspases, cysteine proteinase, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: Porphyromonas gingivalis
• Total number of polymer chains: 1
• Total formula weight: 48805.14

Authors

Eichinger, A.,Beisel, H.-G. (deposition date: 1999-08-24, release date: 2000-03-01, Last modification date: 2024-10-16)

Primary citation

Eichinger, A.,Beisel, H.G.,Jacob, U.,Huber, R.,Medrano, F.J.,Banbula, A.,Potempa, J.,Travis, J.,Bode, W.
Crystal structure of gingipain R: an Arg-specific bacterial cysteine proteinase with a caspase-like fold.
EMBO J., 18:5453-5462, 1999

PubMed 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.

PubMed: 10523290
DOI: 10.1093/emboj/18.20.5453

Experimental method

X-RAY DIFFRACTION (2 Å)