Re: "homology / similarity" of proteins

Dr Alan Mills (
Fri, 24 May 1996 20:58:24 +0100 (BST)

On Fri, 24 May 1996, John Walshaw wrote:
> On Fri, 24 May 1996, William Pitt wrote:
> > John tells me that there are serine proteases with completely different
> > folds but with very similar active site geometry but that this is
> > considered to have occured due to convergent rather than divergent
> > evolution.
> -->8--
> There are two major families in this class, the mammalian trypsin family
> and the bacterial subtilisins, which have very similar active sites, but
> which "..are not otherwise *detectably* related, and provide one of the
> most striking examples of *apparent* evolutionary convergence" (my
> asterisks)- from "Proteins", Creighton. In Branden and Tooze it is
> described as "a classical example of convergent evolution at the molecular
> level".
> I seem to remember reading/hearing somewhere that there may be evidence
> that the two families share a common ancestor with this active site... am
> I remembering correctly? Can anyone offer any insight?
> John Walshaw

It's a useful exercise to look at the linear relationship of the triad of
active site residues, His, Asp, Ser in these two major classes, and to
see where they come in relation to the secondary structural elements in
the two fold types, prokaryotic subtilases, and eukaryotic trypsin-like
serine proteinases. The students should be encouraged to do this for
themselves, and think about "homology" in this context.

A third class of hydrolases which uses a similar His-Asp-Ser catalytic
triad, but which, in general are not proteases, is the so-called
alpha/beta hydrolase family, which are enzymes for a disparate set of
small molecule reactions. The first structure to be elucidated in this
class was that of acetylcholinesterase, by Joel Sussman's group in Israel
before he took up his present post as Head of the PDB at BNL. Perhaps
someone else can weigh in with the appropriate literature refs., and
other members of this family.

The important reason for me banging on about this group is/was the
surprising discovery that the His-Asp-Ser triad were disposed in a
Mirror-Image geometric arrangement compared to the two serine proteinase
familes. I doubt if anyone would seriously suggest that such an
inversion could be arrived at by anything other than convergent evolution.

These 3 classes repay close examination, since they are fairly widespread
in Nature.

Best Regards,

Alan Mills at Venus Internet Ltd, 24 Denmark Street, London WC2H 8NJ, UK web:
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