COCRYSTAL STRUCTURE DATA OF HUMAN CYTOMEGALOVIRUS PROTEASE INHIBITOR COMPLEX

人巨细胞病毒（HCMV）蛋白酶是一种病毒丝氨酸蛋白酶 对蛋白质组装的蛋白水解加工至关重要 巨细胞病毒衣壳成熟的前体。 抑制剂 这种蛋白酶可能潜在地用作抗病毒剂， 治疗移植和免疫功能低下患者的HCMV感染。 最近，HCMV蛋白酶催化结构域apo的X射线结构， Agouron对该酶进行了研究，并发表在Cell，86：835-843（1996）中。 我们采用基于结构的药物设计方法来设计 抑制剂的 利用强同步辐射X射线束，我们可以得到 抑制剂复合物的高分辨率衍射数据。 的 结构信息将有助于结构-活性的合理化 抑制剂的关系，并将有助于设计和优化 疱疹病毒蛋白酶的新抑制剂。

Human cytomegalovirus (HCMV) protease is a viral serine protease essential for proteolytic processing of the assembly of protein precursor during cytomegalovirus capsid maturation. Inhibitors to this protease may potentially be useful as antiviral agents for treating HCMV infection in transplant and immunocompromised patients. Recently, an X-ray structure of the HCMV protease catalytic domain apo enzyme was solved at Agouron and published in Cell, 86:835-843 (1996). We are taking the structure-based drug design approach to design inhibitors. Using the intense synchrotron X-ray beam we can obtain high resolution diffraction data of inhibitor complexes. The structure information will help to rationalize the structure-activity relationships of inhibitors and will aid the design and optimization of new inhibitors against herpesvirus proteases.