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， 与最近发现的一种 人类疱疹病毒（HHV-8）。 HHV-8，也称为卡波西氏病 肉瘤相关疱疹病毒（KSHV），需要活性的 病毒编码的蛋白酶（KSHV Pr）用于其在体内和体内成熟， 细胞培养 这种蛋白酶似乎利用结构和 底物识别基序与其他丝氨酸完全不同 蛋白酶，如胰凝乳蛋白酶和枯草杆菌蛋白酶家族的那些。 这些后一类酶已经被本领域的技术人员广泛研究。 Craik组;这种以前的知识和经验应该有助于 KSHV Pr的结构、底物的分子细节的阐明 识别和催化机制。 结构研究是 目前正在与KSHV Pr合作，并得到CGL资源的帮助。 这 变异酶目前被用来确定 KSHV Pr的三维结构。这一努力将反过来帮助 在基于结构的小分子蛋白酶抑制剂的设计中， KSHV Pr显性负优势种的合理选择。 的 CGL的资源在本研究过程中是非常宝贵的，将 继续为可能的药物开发做出贡献 干预KSHV生命周期的策略。

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.