Guy Brown wrote:
>>We did subject their "perfect enzyme" triose phosphate isomerase to this
>"MCA torture", and found that it was not "perfect" at all - i.e. the
>catalytic step had a significant control coefficient over kcat/Km, thus
>increasing the rate constants of the catalytic step will increase the
>rate at low substrate concentrations, thus the enzyme could evolve to
>be significantly faster.
I think this may just be a matter of what you mean by "significant". It's a
long time since I read the papers, but I remember quite well a seminar that
I heard John Albery give around the time and I'm fairly sure he recognized
then that an improvement by a factor of two or so was quite possible. Are
you claiming more than that?
>>It is interesting to note that "perfect" enzymes in this sense are
>meant to be entirely limited by the substrate binding step,
>whereas the equilibrium binding assumption used in much enzymology/
>transition state theory assumes the opposite - that the catalytic
>step is entirely rate limiting.
>I don't think there is any inconsistency here. As I understand it they were
using evolution along the road towards full binding limitation as their
measure of perfection, so *of course* a "perfect" enzyme will be one that
deviates considerably from traditional textbook assumptions.
As a different point, your term "the equilibrium binding assumption used in
much enzymology/transition state theory assumes the opposite" seems to lump
together rather different sorts of people. Is it really true that people
who apply transition-state theory to enzymes assume equilibrium binding
(who? when? where?), because I don't get much sense of this when I read
Alan Fersht, for example.
athel
Athel Cornish-Bowden
athel at ibsm.cnrs-mrs.frhttp://ir2lcb.cnrs-mrs.fr/~athel/homepage.htm
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