STRUCTURE & FUNCTION ANALYSIS OF KAPOSIS SARCOMA ASSOCIATED PROTEASE: AIDS

卡波西氏肉瘤，一种常见的与艾滋病相关的肿瘤，已经被 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 肉瘤相关疱疹病毒需要协同活动 一种病毒编码的蛋白酶(Pr)及其底物，该组件 蛋白质(AP)。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团队；这些先前的知识应该会对 阐明KSHV Pr的组装、结构和分子细节 底物识别，催化机理。事实上，活跃的， 目前可在Craik实验室获得的纯化酶带来了光明的前景 这些领域的初步进展。此外，两国之间的关系 这与通常合并感染的人类免疫缺陷有关。 病毒正在探索中，小分子的合理设计 和KSHV成熟活性的显性负性抑制因子 公关将以类似的方式进行。在所有这些问题中 酶的结构、机制和抑制剂设计，资源 计算机图形实验室已被证明是一种非常有价值的工具 制定药物策略以减缓癌症的进展 艾滋病患者的卡波西肉瘤。

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 concerted activity of a virally-encoded protease (Pr) and its substrate, the assembly protein (AP). 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 should aid remarkably in the elucidation of the molecular details of KSHV Pr's assembly, structure, substrate recognition, and catalytic mechanism. Indeed, the active, purified enzyme now available in the Craik lab has led to promising initial advances in these areas. In addition, the relationship of this Pr to that of the commonly co-infected human immunodeficiency virus is being explored, and the rational design of small-molecule and dominant-negative inhibitors of the maturational activity of KSHV Pr will be pursued in an analogous fashion. In all these questions of enzyme structure, mechanism, and inhibitor design, the resources of the Computer Graphics Laboratory have proved an invaluable tool for developing pharmaceutical strategies to alleviate the progression of Kaposi's Sarcoma in AIDS patients.