Enzymes as mechanical devices

nvett at ac.dal.ca nvett at ac.dal.ca
Tue May 25 09:06:47 EST 1993

In article <C7H7Bn.HtM at news.otago.ac.nz>, craigm at sanger.otago.ac.nz (Craig Marshall) writes:
> I like the idea very much. The serpins, a group of (mostly) serine
> protease inhibitors have a number of features that I believe are best
> explained by a mechanical analogy. They exist in two forms; an intact
> and active form, and an inactive and cleaved form. Inactivation is
> associated with interaction with an appropriate protease and the
> subsequent slow release of the cleaved inhibitor. The two forms show
> very different thermal stabilities, and most interestingly intact
> serpins show little helical structure as detected by fourier-transform
> infrared spectroscopy. After cleavage helical signal is found. X-ray
> structures of four cleaved (or essentially so) serpins indicate that
> there are definitely helices in the structure. I have imagined that
> the helices act as springs and are thus slightly under or over-wound
> in the intact molecules, and this provides the force that allows the
> substantial changes in structure believed to be associated with the
> inhibitory mechanism. Amongst these is the insertion of a further
> strand into a beta-sheet.
> I would be interested in any other examples that might support (or
> refute) the idea of mechanical enzymes.
> --
>         Craig Marshall          	craigm at sanger.otago.ac.nz or
>         Biochemistry Department 	bioc07 at otago.ac.nz
>         University of Otago     	Phone 64 3 479 7849   	
>         P.O. Box 56             	Fax   64 3 479 7866   	
>         Dunedin, New Zealand                                   	

I have also visualised alpha helices in enzymes as "springs" and the
effect of "unwinding" or over winding these "springs" probably provides
the energy for catalysis and regulatory process dependent conformational
changes.  I think that this is a bit more reasonable than a rigid mechanical
device concept.  However, in the April 29 issue of Nature (Vol 362, pp814-820)
Tilbeurgh et al., describe the crystallization of the lipase-procolipase
complex.  The lipases have their active site "covered" by a "lid" or a 
"flap" which moves away as a result of conformational changes induced on the
molecule as a result of substrate binding.  The flap is a helix and helices are
present in both the "open" and "closed" forms of the molecule but the length
and the residues in the helices differ(unwinding of the original helix and 
formation of two new helices).  In any case, this opening of the molecule
now allows the formation of the oxyanion hole and the orientation of the
catalytic triad residues for catalysis.    This seems to support the "enzymes
as mechanical devices" concept--I think.  What do you think?

Nat Vettakkorumakankav
Department of Biochemistry

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