牙龈卟啉单胞菌
微生物学
蛋白酵素
毒力
半胱氨酸蛋白酶抑制剂
半胱氨酸蛋白酶
生物
蛋白质水解
酶
化学
生物化学
细菌
基因
细胞凋亡
遗传学
程序性细胞死亡
半胱氨酸蛋白酶
作者
Tomoko Kadowaki,Kenji Yamamoto
出处
期刊:Current Protein & Peptide Science
[Bentham Science]
日期:2003-12-01
卷期号:4 (6): 451-458
被引量:28
标识
DOI:10.2174/1389203033486992
摘要
Porphyromonas gingivalis is a Gram-negative anaerobic bacterium that is implicated as a major etiologic agent of adult periodontal disease. This bacterium is asaccharolytic and possesses strong potency for proteolysis. It produces a novel class of cysteine proteinases, termed gingipains, in the cell-associated and secretory forms. Gingipains consist of arginine-X-specific cysteine proteinases (Arg-gingipains, Rgps) and lysine-X-specific cysteine proteinase (Lys-gingipain, Kgp). Previous studies using various P. gingivalis mutants deficient in Rgp- and / or Kgp-encoding genes have revealed that both enzymes are important for the bacterium both to exhibit its virulence and to survive in periodontal pockets. Mammalian internal proteinase inhibitors such as cystatins, α1-antichymotrypsin, and tissue inhibitor of metalloproteinases (TIMPs) have little or no effects on the proteolytic activities of these enzymes, suggesting the evasion of the bacterium from host defense mechanisms. Recent epidemiological reports have shown a significant relation between periodontal diseases and systemic diseases such as cardiovascular diseases and diabetes. Thus, the development of potent inhibitors specific for gingipains provides new therapeutic approaches to treat periodontal diseases and the related systemic diseases. More recently, we have developed novel synthetic inhibitors specific for Rgp and Kgp, based on the specificity and efficacy of cleavage of histatins by each enzyme. We have also isolated a novel and potent inhibitor of Rgp from the culture supernatant of Streptomyces species strain FA-70, now designated as FA-70C1. Here we summarized the usefulness of these new inhibitors in providing a broader application in studies of this important class of enzymes. Keywords: porphyromonas gingivalis, gingipains, arg-gingipains, lys-gingipain, cystatins, antichymotrypsin, metalloproteinases
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