Colworth Medal Lecture. Enzymes in the quantum world.

Abstract

Studies on those enzymes and electron-transfer proteins involved in the catabolism of 'C1' substrates in methylotrophic bacteria have provided a wealth of information concerning the transfer of electrons and hydrogen by quantum tunnelling mechanisms. With regard to H-transfer, studies with MADH have provided the first example of ground-state tunnelling of hydrogen driven by the natural, thermally activated, low-frequency motions of the enzyme molecule. Subsequent studies with related enzymes (e.g. TMADH and bacterial sarcosine oxidase) and with thermophilic alcohol dehydrogenase suggest that vibrationally assisted tunnelling of hydrogen may be more widespread than originally assumed. Our studies of electron transfer in TMADH and ETF have established a role for large-scale protein dynamics in interprotein electron transfer, and have made a contribution to the ongoing debate concerning the mechanism of amine oxidation by enzymes. Moreover, our work has identified a hitherto unknown mechanism for the control of electron density in reduced flavin that influences the rate of electron transfer between redox centres within a protein molecule. Despite this progress, however, many questions still remain to be resolved. With the development of more sophisticated experimental techniques (and also continued financial support from the funding agencies!), the mechanistic uncertainties surrounding the quantum mechanical transfer of electrons and hydrogen in biological molecules should be transmogrified into the certainties one more readily acquaints with the classical world.