Wlodawer A, Gustchina A, Reshetnikova L, Lubkowski J, Zdanov A, Hui K Y, Angleton E L, Farmerie W G, Goodenow M M, Bhatt D
Macromolecular Structure Laboratory, NCI-Frederick Cancer Research and Development Center, Maryland 21702, USA.
Nat Struct Biol. 1995 Jun;2(6):480-8. doi: 10.1038/nsb0695-480.
The crystal structure of a recombinant form of the proteinase encoded by the feline immunodeficiency virus (FIV PR) has been solved at 2 A resolution and refined to an R-factor of 0.148. The refined structure includes a peptidomimetic, statine-based inhibitor, LP-149, which is an even more potent inhibitor of HIV PR. Kinetic parameters were obtained for the cleavage of five substrates by FIV PR, and inhibition constants were measured for four inhibitors. The structure of FIV PR resembles other related retroviral enzymes although few inhibitors of HIV PR are capable of inhibiting FIV PR. The structure of FIV PR will enhance our knowledge of this class of enzymes, and will direct testing of new proteinase inhibitors in a feline animal model.
猫免疫缺陷病毒（FIV PR）编码的蛋白酶重组形式的晶体结构已在2埃分辨率下解析，并精修至R因子为0.148。精修后的结构包含一种基于拟肽、含沙他汀的抑制剂LP - 149，它是一种对HIV PR更有效的抑制剂。获得了FIV PR切割五种底物的动力学参数，并测定了四种抑制剂的抑制常数。FIV PR的结构与其他相关逆转录病毒酶相似，尽管HIV PR的抑制剂很少能够抑制FIV PR。FIV PR的结构将增进我们对这类酶的了解，并指导在猫动物模型中对新型蛋白酶抑制剂进行测试。
