日本研究人员在最新的美国《国家科学院院刊》网络版上报告说，他们成功分析出艾滋病病毒增殖必需的蛋白酶整体构造。
此前研究发现，艾滋病病毒增殖必需的蛋白酶分子中氢原子的位置对蛋白酶的作用能产生重要影响，但确定氢原子的具体位置非常困难。
来自日本原子能研究开发机构和京都药科大学等机构的研究人员首先制造了一种晶体，这种晶体由艾滋病病毒增殖必需的蛋白酶和能使之丧失功能的阻碍剂结合而成，然后研究人员借助穿透力强的中子射线通过分析晶体构造，了解到艾滋病病毒增殖必需的蛋白酶的整体结构，确定了蛋白酶分子中氢原子的位置。
研究人员认为，这次研究将有助于将来研发出更加有效的抗艾滋病药物。（生物谷Bioon.com）
生物谷推荐原始出处：
PNAS，doi: 10.1073/pnas.0809400106，Motoyasu Adachi，Ryota Kuroki
Structure of HIV-1 protease in complex with potent inhibitor KNI-272 determined by high-resolution X-ray and neutron crystallography
Motoyasu Adachia, Takashi Ohharaa, Kazuo Kuriharaa, Taro Tamadaa, Eijiro Honjoa, Nobuo Okazakia, Shigeki Araia, Yoshinari Shoyamaa, Kaname Kimurab, Hiroyoshi Matsumurac,d,e, Shigeru Sugiyamac,d, Hiroaki Adachic,d,e, Kazufumi Takanoc,d,e, Yusuke Moric,d,e, Koushi Hidakaf, Tooru Kimuraf, Yoshio Hayashif, Yoshiaki Kisof and Ryota Kurokia,1
HIV-1 protease is a dimeric aspartic protease that plays an essential role in viral replication. To further understand the catalytic mechanism and inhibitor recognition of HIV-1 protease, we need to determine the locations of key hydrogen atoms in the catalytic aspartates Asp-25 and Asp-125. The structure of HIV-1 protease in complex with transition-state analog KNI-272 was determined by combined neutron crystallography at 1.9-Å resolution and X-ray crystallography at 1.4-Å resolution. The resulting structural data show that the catalytic residue Asp-25 is protonated and that Asp-125 (the catalytic residue from the corresponding diad-related molecule) is deprotonated. The proton on Asp-25 makes a hydrogen bond with the carbonyl group of the allophenylnorstatine (Apns) group in KNI-272. The deprotonated Asp-125 bonds to the hydroxyl proton of Apns. The results provide direct experimental evidence for proposed aspects of the catalytic mechanism of HIV-1 protease and can therefore contribute substantially to the development of specific inhibitors for therapeutic application.
