[Gingipains as the determinants of periodontopathogenicity].
The arginine-specific cysteine proteinase (Arg-gingipain, Rgp) and lysine-specific cysteine proteinase (Lys-gingipain, Kgp) are produced by Porphyromonas gingivalis, an etiological bacterium of periodontal disease. Rgp and Kgp have been implicated as the major virulent factors because of their degrading activity to a broad range of host proteins and of the essential roles in bacterial cell viability. Recent studies have demonstrated the association of P. gingivalis with systemic diseases such as cardiovascular diseases, preterm birth, and low birth weight. The majority of gingipains exist as the membrane-associated complexes composed of the proteinase domains of both Rgp and Kgp, the C-terminal adhesin domains of RgpA and Kgp, phospholipids, and LPS. The complex induced potent viability loss of human endothelial cells and fibroblasts. As the suppression of Rgp and Kgp seems to be the most important to overcome the P. gingivalis-induced systemic disorders as well as the periodontal disease, we have thus designed and synthesized novel proteinase inhibitors specific to Rgp and Kgp on the basis of cleavage sites. Some of them suppressed the characteristic features of P. gingivalis associated with its pathogenicity such as degradation of host proteins, hemagglutination, enhancement of vascular permeability, disruption of leukocytes function, and induction of host cell death.
Kadowaki
Tomoko
T
Department of Pharmacology, Graduate School of Dental Science, Kyushu University, Fukuoka, Japan.
Takii
Ryosuke
R
Baba
Atsuyo
A
Yamamoto
Kenji
K
D018829:Adhesins, Bacterial; D002199:Capillary Permeability; D002318:Cardiovascular Diseases / Q000209:etiology; D003546:Cysteine Endopeptidases; D015195:Drug Design; D004791:Enzyme Inhibitors; D000080867:Gingipain Cysteine Endopeptidases; D006384:Hemagglutination; D006388:Hemagglutinins; D006801:Humans; D009504:Neutrophils / Q000276:immunology; D010510:Periodontal Diseases / Q000382:microbiology*; D010587:Phagocytosis; D016966:Porphyromonas gingivalis / Q000201:enzymology / Q000472:pathogenicity; D011506:Proteins / Q000378:metabolism; D037521:Virulence Factors
D018829:Adhesins, Bacterial; D004791:Enzyme Inhibitors; D000080867:Gingipain Cysteine Endopeptidases; D006388:Hemagglutinins; D011506:Proteins; D037521:Virulence Factors; D003546:Cysteine Endopeptidases