Re: How many genes do we differ on?

Date: Thu Mar 15 2001 - 14:40:40 MST

Robert Bradbury wrote:
> Jim wrote:
> > So the final 3D configuration of a protein, and its resulting
> > function, are quite robust against noise in the 1D sequence?
> It varies a lot with the amino-acid. I think proline and
> cysteine would be good examples of amino acids that you
> can't substitute without breaking things (proline is I
> think essential at certain 2D folds in the protein chain
> and cysteine is essential for forming di-sulfide bonds that
> hold the final 3D structure more rigidly). However many of
> the hydrophobic or hydrophilic amino acids (which probably
> serve to drive local-folding rates) can probably be substituted
> without having too much of an effect on the end result.

One thing to keep in mind is that enzymes work via a large number of very
weak bonds. The active site gets its specificity and selectivity through
having a very close fit to the reactants so that the weak binding forces
will cumulatively have a strong effect. Qualitatively, this suggests that
even minor perturbations which would change the shape of the active site
only slightly could still significantly reduce overall binding energy.

The analogy I have seen (may have been from Nanomedicine) is like a glove
that is carefully hand-tailored to fit just one person. When worn, it
is smooth and supple and barely touches the skin. But if someone else
tries to put it on it binds and pulls and pinches. Make even a slight
change to the glove and it won't fit nearly as well.

It may be that this analogy works better for some enzymes than others.
Some enzymes have a relatively easy job and won't need such a precise
fit to the reactants. These would be more immune to small changes in
the protein. But others have to work harder to catalyze their reactions
and these would be less tolerant of even seemingly minor changes.


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