IUBio

Enzymes!?!

Douglas Kell dbk at aber.ac.uk
Thu Jun 28 04:27:36 EST 2001


I should know better than to respond to this...., but....

Transition state theory (TST) is not the only game in town so far as 
explaining 'how' enzymes work. In fact its chief assumption (a static 
energy barrier) is OBVIOUSLY untrue for the highly fluctuating things 
that enzymes are. The eponymous book edited by Rick Welch covers a 
lot of the early work pointing up alternatives

The Fluctuating Enzyme (ed. Welch, G..R.), John Wiley, New York, 
1986.

If the role of a good theory is to have some predictive power as well 
(I am not sold on this; most often in science the competition between 
theories is actually on the basis of explaining EXISTING facts which 
the party line usually likes - or is forced - to ignore, and there 
are plenty fo precedents even in my own experience...) then theories 
that recognise the role of fluctuations give an obvious explanation 
for the (often substantial) effects of VISCOSITY on k-cat, which TST 
really has nothing to say about.

Scrutton and Sutcliffe at Leicester review more modern alternative 
views based largely on tunnelling. Personally I think these types of 
ideas are right on the button, and that many new approaches that have 
recently become available to enzymologists will make it obvious that 
TST was a seductive but less than optimal way to think about enzyme 
catalysis.

Scrutton, N. S., Basran, J. & Sutcliffe, M. J. (1999). New insights 
into enzyme catalysis - Ground state tunnelling driven by protein 
dynamics. European Journal of Biochemistry 264, 666-671.
Scrutton, N. S. (1999). Enzymes in the quantum world. Biochemical 
Society Transactions 27, 767-779.
Sutcliffe, M. J. & Scrutton, N. S. (2000). Enzyme catalysis: over-the-
barrier or through-the-barrier? Trends in Biochemical Sciences 25, 
405-408.
Sutcliffe, M. J. & Scrutton, M. S. (2000). Enzymology takes a quantum 
leap forward. Philos. Trans. R. Soc. Lond. Ser. A-Math. Phys. Eng. 
Sci. 358, 367-386.

This may liven up the newsgroup...

All the best,
Douglas.

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