Details

Autor(en) / Beteiligte

• Gerlits, Oksana
• Wymore, Troy
• Das, Amit
• Shen, Chen-Hsiang
• Parks, Jerry M.
• Smith, Jeremy C.
• Weiss, Kevin L.
• Keen, David A.
• Blakeley, Matthew P.
• Louis, John M.
• Langan, Paul
• Weber, Irene T.
• Kovalevsky, Andrey

Titel

Long-Range Electrostatics-Induced Two-Proton Transfer Captured by Neutron Crystallography in an Enzyme Catalytic Site

Ist Teil von

• Angewandte Chemie (International ed.), 2016-04, Vol.55 (16), p.4924-4927

Auflage

International ed. in English

Ort / Verlag

Germany: Blackwell Publishing Ltd

Erscheinungsjahr

2016

Link zum Volltext

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• Neutron crystallography was used to directly locate two protons before and after a pH‐induced two‐proton transfer between catalytic aspartic acid residues and the hydroxy group of the bound clinical drug darunavir, located in the catalytic site of enzyme HIV‐1 protease. The two‐proton transfer is triggered by electrostatic effects arising from protonation state changes of surface residues far from the active site. The mechanism and pH effect are supported by quantum mechanics/molecular mechanics (QM/MM) calculations. The low‐pH proton configuration in the catalytic site is deemed critical for the catalytic action of this enzyme and may apply more generally to other aspartic proteases. Neutrons therefore represent a superb probe to obtain structural details for proton transfer reactions in biological systems at a truly atomic level. Neutron crystallography captures a two‐proton transfer in the HIV‐1 protease catalytic site triggered by changes in protonation states of distant amino acid side chains.