Probing coupled motions in enzymatic hydrogen tunnelling reactions.
Much work has gone into understanding the physical basis of the enormous catalytic power of enzymes over the last 50 years or so. Nevertheless, the detailed mechanism used by Nature's catalysts to speed chemical transformations remains elusive. DHFR (dihydrofolate reductase) has served as a paradigm to study the relationship between the structure, function and dynamics of enzymatic transformations. A complex reaction cascade, which involves rearrangements and movements of loops and domains of the enzyme, is used to orientate cofactor and substrate in a reactive configuration from which hydride is transferred by quantum mechanical tunnelling. In the present paper, we review results from experiments that probe the influence of protein dynamics on the chemical step of the reaction catalysed by TmDHFR (DHFR from Thermotoga maritima). This enzyme appears to have evolved an optimal structure that can maintain a catalytically competent conformation under extreme conditions.
Allemann
Rudolf K
RK
School of Chemistry, Cardiff University, Cardiff, UK.
Evans
Rhiannon M
RM
Loveridge
E Joel
EJ
D002384:Catalysis; D006859:Hydrogen / Q000737:chemistry / Q000378:metabolism*; D008958:Models, Molecular; D011487:Protein Conformation; D011789:Quantum Theory; D013762:Tetrahydrofolate Dehydrogenase / Q000737:chemistry / Q000378:metabolism*; D020124:Thermotoga maritima / Q000201:enzymology
D006859:Hydrogen; D013762:Tetrahydrofolate Dehydrogenase