The oral pathogenPorphyromonas gingivalisis a keystone pathogen in the development of chronic periodontitis. Gingipains, the principle virulence factors ofP. gingivalisare multidomain, cell-surface proteins containing a cysteine protease domain. The lysine specific gingipain, Kgp, is a critical virulence factor ofP. gingivalis. We have determined the X-ray crystal structure of the lysine-specific protease domain of Kgp to 1.6 Å resolution. The structure provides insights into the mechanism of substrate specificity and catalysis.