Structural Analysis of Inhibitor Binding Site of Enzyme by Neutron Crystallography

人免疫缺陷病毒蛋白酶-I（HIVPR）是治疗艾滋病的重要药物靶蛋白之一。为了有效地发现药物，获得HIVPR活性位点结合水分子的结构信息对于有效抑制剂的结合是重要的。 由于HIVPR涉及自降解，因此设计了单链和交联HIVPR。制备了两种HIVPR，并用X-射线晶体学方法测定了它们的三级结构。所设计的HIV-PR将有助于从动力学和热力学角度评价新设计的抑制剂的亲和力，以及制备用于中子晶体学的大晶体。

Human immune deficiency virus protease–I (HIVPR) is one of the important drug target proteins for the acquired immune deficiency syndrome. For the efficient drug discovery, it is of importance to obtain structural information of bound water molecules at the active site of HIVPR for the binding of potent inhibitors. Since HIVPR involves the self-degradation, the single-chained and cross-linked HIVPR were designed. The both HIVPR were prepared, and their tertiary structure was determined by X-ray crystallography. The designed HIV-PR will be useful for evaluate the affinity of newly designed inhibitors from kinetic and thermodynamic point of view and preparation of large crystal for neutron crystallography.