日本研究人員在最新的美國《國家科學(xué)院院刊》網(wǎng)絡(luò)版上報告說,，他們成功分析出艾滋病病毒增殖必需的蛋白酶整體構(gòu)造,。
此前研究發(fā)現(xiàn)，艾滋病病毒增殖必需的蛋白酶分子中氫原子的位置對蛋白酶的作用能產(chǎn)生重要影響,，但確定氫原子的具體位置非常困難。
來自日本原子能研究開發(fā)機(jī)構(gòu)和京都藥科大學(xué)等機(jī)構(gòu)的研究人員首先制造了一種晶體，這種晶體由艾滋病病毒增殖必需的蛋白酶和能使之喪失功能的阻礙劑結(jié)合而成,，然后研究人員借助穿透力強(qiáng)的中子射線通過分析晶體構(gòu)造，了解到艾滋病病毒增殖必需的蛋白酶的整體結(jié)構(gòu),，確定了蛋白酶分子中氫原子的位置,。
研究人員認(rèn)為，這次研究將有助于將來研發(fā)出更加有效的抗艾滋病藥物,。（生物谷Bioon.com）
生物谷推薦原始出處：
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.
