BACTERIAL PROTEINASES IN PERIODONTAL DISEASE

描述：牙周病是一种混合感染，主要涉及 龈沟和/或牙周袋的定植 牙龈卟啉单胞菌（P. gingivalis）。 这种细菌产生 大量的半胱氨酸类蛋白酶，这些被认为是 负责直接和间接的退化， 牙周袋内的结缔组织结构。 两个主要 牙龈卟啉单胞菌释放的蛋白酶，一种与Arg-X，另一种与Arg-X， Lys-X特异性，已被纯化，并建议负责 补体、激肽释放酶和凝血功能失调 瀑布，并作为一个结果，增加了裂隙流，流血 探测和中性粒细胞积聚，这些是牙周炎的标志。 对它们的一级结构的分析表明，每种蛋白酶都是 合成为大的多聚蛋白前体，其被加工成 非共价连接的复合物，其含有催化结构域和推定的 粘附/血凝结构域。 这项建议的具体目标是 设计1）进一步阐明这些酶在破坏 纤维蛋白溶解的调节和宿主蛋白酶的控制，2） 为了表征每种蛋白酶的粘附/血凝素结构域，3） 研究每种蛋白酶从其高水平成熟的机制， 分子量多蛋白前体形式，4）确定作用 各蛋白酶在P. 牙龈炎，和5）开始合作调查，以确定 针对每种蛋白酶生产的疫苗是否有用 治疗学

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.