[Protein-analysis] Re: Question about enzymes

lucasea from sbcglobal.net via proteins%40net.bio.net (by lucasea from sbcglobal.net)
Tue Oct 17 21:34:32 EST 2006

"Tom Anderson" <twic from urchin.earth.li> wrote in message 
news:Pine.LNX.4.62.0610171928500.24308 from urchin.earth.li...
> - the mammalian fatty acid synthase, a homodimer which catalyses no less 
> than four reactions [1]

Just curious (this is an honest question), are these four reactions 
catalyzed by four different active sites?  I'm not a biochemist, but I 
understand it's not uncommon for a particular active site to catalyze 
multiple different reactions that have similar mechanistic requirements, 
particularly if the binding pocket isn't too tight/selective.

> Because, having looked at more enzymes than you can shake a 
> spectrophotometer at, biochemists have observed that most do only have one 
> active site. And why is that? Good question; i'm not aware that there's a 
> definitive answer, and not sure that there even could be one.

Again, not the opinion of a biochemist, but I suspect it's basically a 
probability/entropic argument.  I suspect that the chances of a new function 
arising in a pre-existing enzyme the has some other function without 
destroying that original function is less than the function arising in a new 
protein or than the new function arising in the original enzyme but at the 
same time destroying the original function of that enzyme.  Certainly 
there's a finite probability that a mutation that helps form the second 
active site in a pre-existing enzyme will destroy the function of the 
original active site by changing the tertiary structure in the wrong way. 
Intuition also tells me that it would be a low entropy configuration to have 
two active sites in a single enzyme, as compared to the same two active 
sites in two separate enzymes.  Maintaining this lower-entropy configuration 
costs the organism more free energy, and that's usually not in the best 
interests of the organism, evolutionarily speaking.

These are just the intuitions of a physical organic chemist with a 
smattering of understanding of biochemistry, but I do understand that 
evolution can behave in counter-intuitive ways.

Eric Lucas 

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