Refine your search:     
Report No.

Structure of HIV-1 protease in complex with potent inhibitor KNI-272 determined by high-resolution X-ray and neutron crystallography

Adachi, Motoyasu; Ohara, Takashi   ; Kurihara, Kazuo; Tamada, Taro; Honjo, Eijiro; Okazaki, Nobuo; Arai, Shigeki; Shoyama, Yoshinari; Kimura, Kaname*; Matsumura, Hiroyoshi*; Sugiyama, Shigeru*; Adachi, Hiroaki*; Takano, Kazufumi*; Mori, Yusuke*; Hidaka, Koshi*; Kimura, Toru*; Hayashi, Yoshio*; Kiso, Yoshiaki*; Kuroki, Ryota

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 Asp25 and Asp125. The structure of HIV-1 protease in complex with transition-state analog KNI-272 was determined by combined neutron crystallography at 1.9 ${AA}$ resolution and X-ray crystallography at 1.4 ${AA}$ resolution. The resulting structural data shows that the catalytic residue Asp25 is protonated and that Asp125 is deprotonated. The proton on Asp25 makes a hydrogen bond with the carbonyl group of the allophenylnorstatine group in KNI-272. The deprotonated Asp125 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.



- Accesses




Category:Multidisciplinary Sciences



[CLARIVATE ANALYTICS], [WEB OF SCIENCE], [HIGHLY CITED PAPER & CUP LOGO] and [HOT PAPER & FIRE LOGO] are trademarks of Clarivate Analytics, and/or its affiliated company or companies, and used herein by permission and/or license.