Gustchina A, Weber I T
Crystallography Laboratory, NCI-Frederick Cancer Research and Development Center, MD 21701.
FEBS Lett. 1990 Aug 20;269(1):269-72. doi: 10.1016/0014-5793(90)81171-j.
The crystal structure of HIV-1 protease with an inhibitor has been compared with the structures of non-viral aspartic proteases complexed with inhibitors. In the dimeric HIV-1 protease, two 4-stranded beta-sheets are formed by half of the inhibitor, residues 27-29, and the flap from each monomer. In the monomeric non-viral enzyme the single flap does not form a beta-sheet with an inhibitor. The HIV-1 protease shows more interactions with a longer peptide inhibitor than are observed in non-viral aspartic protease-inhibitor complexes. This, and the large movement of the flaps, restricts the conformation of the protease cleavage sites in the retroviral polyprotein precursor.
已将含有抑制剂的HIV-1蛋白酶的晶体结构与与抑制剂复合的非病毒天冬氨酸蛋白酶的结构进行了比较。在二聚体HIV-1蛋白酶中，抑制剂的一半、27-29位残基以及每个单体的侧翼形成了两个4股β折叠。在单体非病毒酶中，单个侧翼不会与抑制剂形成β折叠。与非病毒天冬氨酸蛋白酶-抑制剂复合物相比，HIV-1蛋白酶与更长的肽类抑制剂表现出更多的相互作用。这一点以及侧翼的大幅移动限制了逆转录病毒多蛋白前体中蛋白酶切割位点的构象。
