tailieunhanh - Báo cáo Y học: A new conceptual framework for enzyme catalysis Hydrogen tunneling coupled to enzyme dynamics in flavoprotein and quinoprotein enzymes

Recent years have witnessed high levels of activity in identifying enzyme systems that catalyse H-transfer by quantum tunneling. Rather than being restricted to a small number of specific enzymes as perceived initially, it has now become an accepted mechanism for H-transfer in a growing number of enzymes. Furthermore, H-tunneling is driven by the thermally induced dynamics of the enzyme. In some of those enzymes that break stable C–H bonds the reaction proceeds purely by quantum tunneling, without the need to partially ascend the barrier. Enzymes studied that fall into this category include the flavoprotein and quinoprotein amine dehydrogenases, which have. | Eur. J. Biochem. 269 3096-3102 2002 FEBS 2002 doi MINIREVIEW A new conceptual framework for enzyme catalysis Hydrogen tunneling coupled to enzyme dynamics in flavoprotein and quinoprotein enzymes Michael J. Sutcliffe1 2 and Nigel S. Scrutton1 Departments of1 Biochemistry and 2Chemistry University of Leicester UK Recent years have witnessed high levels of activity in identifying enzyme systems that catalyse H-transfer by quantum tunneling. Rather than being restricted to a small number of specific enzymes as perceived initially it has now become an accepted mechanism for H-transfer in a growing number of enzymes. Furthermore H-tunneling is driven by the thermally induced dynamics of the enzyme. In some of those enzymes that break stable C-H bonds the reaction proceeds purely by quantum tunneling without the need to partially ascend the barrier. Enzymes studied that fall into this category include the flavoprotein and quinoprotein amine dehydrogenases which have proved to be excellent model systems. These enzymes have enabled us to study the rela tionship between barrier shape and reaction kinetics. This has involved studies with slow and fast substrates and enzymes impaired by mutagenesis. A number of key questions now remain including the nature of the coupling between protein dynamics and quantum tunneling. The wide-ranging implications of quantum tunneling introduce a paradigm shift in the conceptual framework for enzyme catalysis inhibition and design. Keywords H-tunneling transition state theory protein dynamics flavoprotein quinoprotein kinetic isotope effect computational simulation quantum mechanics stopped-flow kinetics molecular mechanics. INTRODUCTION The text-book description of catalysis states that enzymes reduce the energy required to surmount the barrier between reactants and products which leads to enhanced rates. This classical over-the-barrier treatment known as transition state theory TST has been used to depict .