[Protein-analysis] Re: why cant we say chaperone an enzyme?

Dr Engelbert Buxbaum engelbert_buxbaum at hotmail.com
Tue Apr 25 12:18:46 EST 2006

DK wrote:

> >I agree. At the very least many of them are ATPases. Of course, the
> >chaperone activity (unlike chaperonins) is not enzymatic, as no reaction
> >is catalysed. 
> I am not sure even about that. Surely it's a matter of definitions
> but I'd argue that even in the most general case protein folding 
> is definitely catalyzed by chaperones, with a pretty typical reaction 
> mechanism, transition state, etc. The boundary seems arbitrary 
> and semantic. What's one covalent bond over many H-bonds
> and salt bridges? 

But chaperones do not unfold mis-folded protein (as chaperonins do) nor
do they catalyse folding. They simply bind to their clients and thereby
prevent them from miss-folding. The comparison with the human chaperone
is apt: They prevent inappropriate interactions, but do not (should not)
help in forming appropriate ones. The correct folding is attained
without the help of chaperones or even chaperonins, the latter form an
"Anfinsen-cage" where folding can happen in isolation, without the risk
of aggregation. The concepts of prevention of miss-folding (both
chaperones and chaperonins), of unfolding miss-folded proteins
(chaperonins only) and of catalysing folding (neither) need to be
carefully distinguished. 

Something different is the transport activity of chaperones like
Hsp70/Hsc70: With ATPase-stimulating factor at the source and
ADP/ATP-exchange factor at the target structure you get vectorial
transport of client proteins which could be considered a catalytic

> In a narrow sense, many proteins form disulfides and that too 
> is catalyzed by chaperones. So here we definitely have 
> intramolecular chemical reaction. 

Yes, of course there is no doubt that protein disulphide isomerases (or
peptidyl prolyl cis/trans-isomerases for that matter) are enzymes, but
they are no chaperones. A chaperone may hold the client protein for the
PDI or PPI to work on (Hsp90 or Bip for example), it is then like a lath
on which different tools may be used. But the actual work is done by the
tool, not the lath.

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