An analysis of reaction pathways for proton tunnelling in methylamine dehydrogenase.
Computational methods have now become a valuable tool to understand the way in which enzymes catalyse chemical reactions and to aid the interpretation of a diverse set of experimental data. This study focuses on the influence of the condensed-phase environment structure on proton transfer mechanisms, with an aim to understand how C-H bond cleavage is mediated in enzymatic reactions. We shall use a combination of molecular simulation, ab initio or semi-empirical quantum chemistry and semi-classical multidimensional tunnelling methods to consider the primary kinetic isotope effects of the enzyme methylamine dehydrogenase (MADH), with reference to an analogous application to triosephosphate isomerase. Analysis of potentially reactive conformations of the system, and correlation with experimental isotope effects, have highlighted that a quantum tunnelling mechanism in MADH may be modulated by specific amino acid residues, such as Asp428, Thr474 and Asp384.
Nuñez
Sara
S
School of Chemistry, University of Manchester, Manchester M13 9PL, UK.
Tresadern
Gary
G
Hillier
Ian H
IH
Burton
Neil A
NA
D002244:Carbon / Q000737:chemistry; D006859:Hydrogen / Q000737:chemistry; D007700:Kinetics; D008956:Models, Chemical; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000737:chemistry*; D011522:Protons; D014305:Triose-Phosphate Isomerase / Q000737:chemistry
D011522:Protons; D002244:Carbon; D006859:Hydrogen; C021567:methylamine dehydrogenase; D000587:Oxidoreductases Acting on CH-NH Group Donors; D014305:Triose-Phosphate Isomerase