Structure of a HIV-1 Protease-Inhibitor Complex determined at 1.1A resolution

0191688 - UMG-J 20033203 RIV DE eng C - Konferenční příspěvek (zahraniční konf.)
Brynda, Jiří - Řezáčová, Pavlína - Štouračová, Renata - Fábry, Milan - Hradilek, Martin - Souček, Milan - Konvalinka, Jan - Sedláček, Juraj
Structure of a HIV-1 Protease-Inhibitor Complex determined at 1.1A resolution.
9th International Conference on the crystallization of Biological Macromolecules. Jena: Jena, 2002, s. -.
[International Conference on the crystallization of Biological Macromolecules /9./. Jena, Německo (DE), 23.03.2002-28.03.2002]
Výzkumný záměr: CEZ:AV0Z4055905; CEZ:AV0Z5052915
Klíčová slova: Structure of a HIV-1 * protease * Inhibitor complex
Kód oboru RIV: EB - Genetika a molekulární biologie

Crystallization conditions for an HIV-1 protease-inhibitor complwx were optimized to produce superior crystals for X-ray diffraction experiments. The X-ray structure of the HIV-1 protease complex was solved and regined at 1.16 A resoluton. In contrast to Saquinavir, the minetic hydroxy group of the inhibitor Z-Pns-Phe-Glu-Glu-NH2 is placed asymmetrically with respect to the non-ctystallographic twofold axis of the protease dimer so that hydrogen bonds between the carbonyl 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 Gly1027, Gly2027, Asp 1025, Asp2025 and via the buried water molecule W7001 to lle 1050 and lle2050. Factors contributing to unusually high, 1.16 a, resolution (e.g. new crystal packing, binding of second molecule of Z-Pns-Phe-Glu-Glu-Nh2, etc.) will discussed.
Trvalý link: http://hdl.handle.net/11104/0087425