Page 51 - Visions of the Future Chemistry and Life Science

40 M. J. SUTCLIFFE AND N. S. SCRUTTON

dehydrogenase has indicated that, under certain conditions (and contrary to
current dogma), ground state tunnelling occurs even when the kinetic
isotope effect
7. This observation lends support to the validity of vibra-
tionally enhanced ground state tunnelling theory in describing enzymatic
hydrogen tunnelling.

2.9 Significance of hydrogen tunnelling in enzymes
Both methylamine dehydrogenase and trimethylamine dehydrogenase cat-
alyse the breakage of stable C–H bonds. These are difficult reactions if
viewed in terms of the classical transition state theory approach to cataly-
sis, but the structural plasticity of methylamine dehydrogenase and tri-
methylamine dehydrogenase (in common with other enzymes) provides a
means of circumventing this problem by facilitating ground state tunnel-
ling. Vibration driven ground state tunnelling may therefore be a common
mechanism for the breakage of C–H bonds by enzymes and this may extend
to other types of hydrogen transfer reactions.
The dynamic barrier approach to catalysis has major implications for
how hydrogen transfer reactions – and indeed other reactions – are mod-
elled theoretically. Given the dynamic nature of protein molecules, it is
perhaps surprising that the indiscriminate use of transition state theory
has persisted for so long. For classical transfers, Kramers’ theory seems
appropriate, and this is an excellent platform from which to develop theo-
ries of quantum tunnelling in enzymes. For those reactions that proceed by
quantum tunnelling, it is the energy barrier width that is important in
determining reaction rate. Tunnelling probability depends on the mass of
the transferred particle, the net driving force and the height and width of
the reaction barrier. Proteins can facilitate this by (i) reduction of mass (e.g.
exclusion of water), (ii) an equalisation of energy states for reactants and
products and, most importantly, (iii) a reduction in barrier width.
Exclusion of water from enzyme active sites is achieved readily and docu-
mented amply in the literature. The exploitation of protein dynamics to
equalise energy states and shorten tunnelling distance is, however, less
well appreciated but nevertheless pivotal.

2.10 Enzymology in the future
An in-depth understanding of biological catalysis is central to the success-
ful exploitation of enzymes by mankind. At the end of the last century the