Petr Kuzmic wrote:
>I suppose everybody remembers Knowles' et al. 1980s work on the
>energetics of the "perfect enzyme".
>Maybe the horrendous formalism that Knowles at al. invented for their
>"perfect enzyme" work could be subjected to yet another kind of torture,
>and cast in terms of MCA??
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. Thus the normal criteria used for catalytic
perfection (a kcat/Km "approching" the diffusion limit) can be
misleading. We have also subjected 3 beta-lactamases (which have
been claimed to be perfect using similar criteria) to similar
torture, and found them to be similarly less than perfect.
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.
Dr Guy C. Brown
Department of Biochemistry,
University of Cambridge,
Tennis Court Road,
Cambridge CB2 1QW, UK.
Tel: (44) (0)1223 333342
Fax: (44) (0)1223 333345
e-mail: gcb at mole.bio.cam.ac.ukhttp://www.bio.cam.ac.uk/dept/biochem/brown
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