Why "alanine" scanning?

Vladimir Svetlov svetlov at oncology.wisc.edu
Mon Oct 20 18:28:26 EST 1997

In article <625n3p$8a6 at panix.com>, iayork at panix.com (Ian A. York) wrote:

> My boss just asked me this, and I didn't have a very satisfactory answer: 
> Why, when doing alanine scanning, does one change to alanine instead of
> glycine?  I understand that alanine is sort of a generic, unexciting, Joe
> Amino Acid; but why isn't glycine just as bland, boring, and unexciting?
> I mumbled about maybe having a sidechain made alanine a little more
> generic than glycine, but I couldn't come up with a clear justification.
> Anyone?

   Glycine (G) ain't got much of side chain at all and is actually prone to
induce turns on insertions, that's why it is not a good choice for a
structurally "neutral" amino acid. 
   For quite some time Alanine (A) was assumed to be a sorta
"non-disruptive" residue, as being small and possessing high propensity
towards alpha-helical structures (actually its the only side chain that
does not have a negative entropic cost of alpha helix formation). There are
two problems with that assumption, however. Firstly, the idea of A being a
structurally inobtrusive substitution was recently challenged both
experimentally (e.g. by Sauer finding all kinds of structural, functional
and stability A-substituted mutants in a massive screen) and theoretically
(e.g. by Ptytsyn's analysis of effects of "forcing" A into hydrophobic
interior instead of a bulky hydrophobic residue). 
On the other hand, A-scanning mutagenesis of the interaction surfaces often
yields but a little (see Ebright for TBP scanning) - that's why in order to
get more informational bang for the mutagenic buck some use "radical"
mutagenesis (substitution for something outrageous and non-recommended by
the Surgeon General, like R, K or Y). 

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