BACTERIAL PROTEINASES IN PERIODONTAL DISEASE

牙周疾病中的细菌蛋白酶

• 批准号: 2015078
• 负责人: James Travis
• 金额: $ 19万
• 依托单位: UNIVERSITY OF GEORGIA
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-08-01 至 2001-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2015078
• 关键词: Bacteroides gingivalis; cell adhesion; endopeptidases; enzyme biosynthesis; enzyme induction /repression; enzyme mechanism; enzyme structure; fibrinolysis; host organism interaction; human tissue; kallikreins; laboratory mouse; laboratory rabbit; periodontitis; posttranslational modifications; protease inhibitor; protein purification; virulence; zymogens

DESCRIPTION: Periodontal disease is a mixed infection, primarily involving colonization of the gingival sulcus and/or the periodontal pocket by the organism Porphyromonas gingivalis (P. gingivalis). This bacterium produces significant quantities of cysteine-class proteinases, and these are believed to be responsible for both the direct and indirect degradation of the connective tissue structure within the periodontal pocket. Two of the major proteinases released by P. gingivalis, one with Arg-X and the other with Lys-X specificity, have been purified and are suggested to be responsible for the dysregulation of the complement, kallikrein, and coagulation cascades, and as a result the increased crevicular flow, bleeding on probing, and neutrophil accumulation which are hallmarks of periodontitis. Analysis of their primary structure indicates that each proteinase is synthesized as a large polyprotein precursor which is processed into a non-covalently linked complex containing a catalytic domain and a putative adhesion/hemagglutination domain. The Specific Aims of this proposal are designed 1) to further elucidate the role of these enzymes in disrupting both the regulation of fibrinolysis and the control of host proteinases, 2) to characterize the adhesion/hemagglutinin domains of each proteinase, 3) to investigate the mechanism(s) of maturation of each proteinase from its high molecular weight poly-protein precursor form, 4) to determine the role of each proteinase in the adhesion and invasion of host epithelial cells by P. gingivalis, and 5) to begin a collaborative investigation to determine whether vaccines produced against each proteinase might be useful therapeutics.

描述：牙周病是一种混合感染，主要涉及 牙龈沟和/或牙周袋的定植 牙龈卟啉单胞菌(P.gigivalis)这种细菌产生 大量的半胱氨酸类的蛋白酶，这些被认为 对环境的直接和间接退化负责 牙周袋内的结缔组织结构。其中两大专业 牙龈假单胞菌释放的蛋白酶，一个含有Arg-X，另一个含有Arg-X Lys-X的特异性，已经被提纯，建议对 对补体、激肽释放酶和凝血功能的失调 级联，结果是增加的缝隙血流，出血 牙周探诊、中性粒细胞堆积是牙周炎的特征。 对它们的一级结构的分析表明，每种蛋白酶都是 作为大的多蛋白前体合成，加工成 含有催化域和推定的 粘附区/血凝区。这项提议的具体目的是 设计1)以进一步阐明这些酶在破坏 纤溶的调节和宿主酶的控制，2) 为了表征每种蛋白酶的黏附/血凝素结构域，3) 从酶活力的高度探讨各酶的成熟机制(S) 分子量多蛋白前体形式，4)测定其作用 各种蛋白水解酶在P。 以及5)开始合作调查，以确定 针对每种酶生产的疫苗是否有用 治疗学。