Page 41 - Visions of the Future Chemistry and Life Science

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

tunnelling gives a transfer distance of 0.6 10 10 m. This distance is similar
to the length of a reaction coordinate and is thus suggestive of high tunnel-
ling probability. The larger masses of deuterium and tritium lead to corre-
sponding transfer distances of 0.4 10 10 m and 0.3 10 10 m, respectively,
thus making kinetic isotope effect studies attractive for the detection of
hydrogen tunnelling in enzymes. Tunnelling is also favoured by high and
narrow energy barriers; for low and wide barrier shapes, transfer is domi-
nated by the classical route.
Thus, different strategies are required for optimising enzyme structure
for reactions to proceed by quantum tunnelling rather than classical trans-
fer. For classical transfers, the enzyme has evolved to reduce the height of
the potential energy barrier and to stabilise the transition state (rather than
ground state). In the quantum regime, it is reduction of barrier width and
not height that optimises rate. Quantum tunnelling from the ground state
requires little or no structural reorganisation of the substrate, and the need
to stabilise a transition state is thus eliminated. Exclusion of water from
the active sites of enzymes prevents coupling of solvent motion to the
transfer reaction, and this leads to a reduction of mass for the transferred
particle. In the following sections, we review the evidence for quantum
tunnelling in biological catalysis and discuss the strategies employed by
enzymes to optimise the transfer process. Surprisingly – and unlike for bio-
logical electron transfers – reports of hydrogen tunnelling in enzymatic
reactions have been restricted to only a small number of enzyme mole-
cules. The realisation that hydrogen tunnelling occurs in enzymes has
been relatively recent. This may, in part, be due to (i) the misconception
that the much larger mass of the hydrogen nucleus is inconsistent with
tunnelling, and (ii) the erroneous assumption that measured kinetic
isotope effects
7 are always indicative of classical hydrogen transfer. Our
recent work has demonstrated that hydrogen tunnelling in proteins is inex-
tricably coupled to protein dynamics. This provides a link to the estab-
lished theories for electron tunnelling in proteins. To provide a framework
for the discussion of hydrogen tunnelling in enzymes, protein-mediated
electron transfer is discussed below.

2.5 Electron tunnelling in proteins

The transfer of electrons in proteins by a quantum mechanical tunnelling
mechanism is now firmly established. Electron transfer within proteins