STRUCTURE & FUNCT ANALYSIS OF KAPOSIS SARCOMA ASSOC HERPESVIRUS PROTEASE: AIDS

卡波西肉瘤是一种常见的艾滋病相关肿瘤，一直以来都是 与新近发现的一种 人类疱疹病毒(HHV-8)。HHV-8，也被称为卡波西病毒 肉瘤相关疱疹病毒(KSHV)，需要一种 病毒编码的蛋白酶(KSHV Pr)在体内和体内成熟的研究 细胞培养。这种蛋白水解酶似乎利用结构和 底物识别基序与其他丝氨酸非常不同 蛋白水解酶，如凝乳酶和枯草杆菌酶家族。 这些后几类酶已经被广泛研究 Craik集团；这种先前的知识和经验应该有助于 阐明KSHV Pr的结构、底物的分子细节 识别和催化机理。结构研究是 目前正在与KSHV公关合作，得到CGL资源的帮助。这 变异酶目前被用来确定 KSHV Pr.的三维结构这一努力反过来将有助于 在基于结构的小分子蛋白酶抑制剂设计中 合理选择显性-负性KSHV Pr种。这个 CGL的资源在本课程中是无价的，并将 继续为可能的药剂学的发展做出贡献 干预KSHV生命周期的战略。

Kaposi's sarcoma, a common AIDS-associated neoplasm, has been correlated with the infection and replication of a recently identified human herpesvirus (HHV-8). HHV-8, also known as Kaposi's sarcoma-associated herpesvirus (KSHV), requires the activity of a virally encoded protease (KSHV Pr) for its maturation in vivo and in cell culture. This protease appears to utilize structural and substrate recognition motifs quite different from other serine proteases, such as those of the chymotrypsin and subtilisin families. These latter classes of enzymes have been extensively studied by the Craik group; such previous knowledge and experience should aid in elucidation of the molecular details of KSHV Pr's structure, substrate recognition, and catalytic mechanism. Structural studies are currently underway with KSHV Pr, aided by the resources of CGL. This variant enzyme is currently being used to determine the three-dimensional structure of KSHV Pr. This effort will in turn aid in the structure-based design of small molecule protease inhibitors and the rational selection of dominant-negative KSHV Pr species. The resources of CGL are invaluable in this course of study and will continue to contribute to the development of possible pharamacuetical strategies to intervene in the KSHV life cycle.