On Aug 27, 4:11pm, Jim Reid wrote:
> Subject: Model enzyme systems?
> What do you think - have advances in enzymology come about through intense
> study of a small group of 'zymes? Have any particular enzymes groups
> tended to be especially suitable for developing certain methods?
> In MCA have certain pathways been studied more extensively than others?
> Given that that is the case (-Grin-) is this as experimental data is more
> widely available for some paths than others, or that they are more
> experimentally accessable, or theoretically tractable?
>-- End of excerpt from Jim Reid
Yes to both questions. Glycolysis has been extensively studied both
experimentally and theoretically and has been studied many times using MCA
(e.g. Heinrich, Cornish-Bowden, and me). Most of the enzymes of this pathway
have been studied extensively. The work of Jeremy Knowles at Harvard on TPI
(triose phosphate isomerase) especially comes to mind. Knowles showed that the
rate constants for the bimolecular steps in the TPI catalytic cycle were well
matched to the rates of diffusion of substrates to the active site. That is,
the enzyme had evolved to a state of "perfection" (Knowles' term) as the
reaction could not be catalyzed to occur any faster, being limited by
diffusion. Roberta Coleman's work at the University of Delaware showed that
isocitrate dehydrogenase undergoes a sequence of conformational changes as the
substrates are added, progressing from an open bowl-like configuration and
eventually enclosing the active site in a protein globe that excludes solvent
(i.e., water). X-ray diffraction studies of glycogen phosphorylase with and
without bound substrate showed comparable conformational changes. The examples
are too numerous to cite. In short, Nature is conservative, studies have shown
that similar molecular mechanisms are used repeatedly to solve similar
bio;chemical problems.
--
Michael C. Kohn
Laboratory of Computational Biology and Risk Analysis
National Institute of Environmental Health Sciences
P.O. Box 12233, Mail Drop A3-06
Research Triangle Park, NC 27709-2233
Telephone:
919-541-4929 (voice)
919-541-1479 (fax)
e-mail:
kohn at valiant.niehs.nih.gov
Web site:
http://valiant.niehs.nih.gov
