A distinct binding mode of a hydroxyethylamine isostere inhibitor of HIV-1 protease

被引:15
作者
Dohnálek, J
Hasek, J
Dusková, J
Petroková, H
Hradilek, M
Soucek, M
Konvalinka, J
Brynda, J
Sedlácek, J
Fábry, M
机构
[1] Acad Sci Czech Republ, Inst Macromol Chem, CR-16206 Prague 6, Czech Republic
[2] Acad Sci Czech Republ, Inst Organ Chem & Biochem, Prague 16610 6, Czech Republic
[3] Acad Sci Czech Republ, Inst Genet Mol, CR-16206 Prague 6, Czech Republic
来源
ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY | 2001年 / 57卷
关键词
D O I
10.1107/S0907444900018928
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
Crystallization conditions for an HIV-1 protease-inhibitor complex were optimized to produce crystals suitable for X-ray diffraction experiments. The X-ray structure of the HIV-1 protease complex was solved and refined at 3.1 Angstrom resolution. In contrast to Saquinavir, the mimetic hydroxy group of the inhibitor Boc-Phe-Psi[(S)-CH(OH)CH2-NH]-Phe-Glu-Phe-NH2 is placed asymmetrically with respect to the non-crystallographic twofold axis of the protease dimer so that hydrogen bonds between the amino group of the inhibitor and the catalytic aspartates can be formed. The inhibitor binds in the centre of the active site by a compact network of hydrogen bonds to Gly27, Gly127, Asp25, Asp125 and via the buried water molecule W301 to Ile50 and Ile150.
引用
收藏
页码:472 / 476
页数:5
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