tailieunhanh - Báo cáo khoa học: Structural and mechanistic aspects of flavoproteins: probes of hydrogen tunnelling

At least half of all enzyme-catalysed reactions are thought to involve a hydrogen transfer. In the last 10 years, it has become apparent that many of these reactions will occur, in part, or in full, by quantum mechanical tunnelling. We are particularly interested in the role of promoting vibra-tions on H transfer, and the Old Yellow Enzyme family of flavoproteins has proven to be an excellent model system with which to examine such reactions. | MINIREVIEW Structural and mechanistic aspects of flavoproteins probes of hydrogen tunnelling Sam Hay Christopher R. Pudney and Nigel S. Scrutton Manchester Interdisciplinary Biocentre and Faculty of Life Science University of Manchester UK Keywords high pressure H-tunneling kinetic isotope effect kinetic isotope fractionation multiple reactive conformations Old Yellow Enzyme promoting vibration protein dynamics quantum mechanics stopped-flow kinetics Correspondence N. S. Scrutton Manchester Interdisciplinary Biocentre and Faculty of Life Science University of Manchester 131 Princess Street Manchester M1 7ND UK Fax 44 161 306 8918 Tel 44 161 306 5152 E-mail Received 23 December 2008 revised 28 April 2009 accepted 1 May 2009 doi At least half of all enzyme-catalysed reactions are thought to involve a hydrogen transfer. In the last 10 years it has become apparent that many of these reactions will occur in part or in full by quantum mechanical tunnelling. We are particularly interested in the role of promoting vibrations on H transfer and the Old Yellow Enzyme family of flavoproteins has proven to be an excellent model system with which to examine such reactions. In this minireview we describe new and established experimental methods used to study H-tunnelling in these enzymes and we consider some practical issues important to such studies. The application of these methods has provided strong evidence linking protein dynamics and H-tun-nelling in biological systems. Introduction There is now fairly widespread recognition that enzyme-catalysed C-H bond cleavage reactions can occur by quantum mechanical tunnelling 1-5 . The role of protein dynamics in these reactions is still hotly debated and it has been proposed that promoting vibrations nonequilibrated fast sub-ps dynamics could modify the reaction barrier and profoundly influence the reaction rate 4 6-12 . In recent years we have investigated H-transfer