VERY, very common in the Pharma setting where we do hundreds of
ligand-bound structures on a given target. Other permutations of this
scenario, such as only one monomer's ligand displacing a ligand used for
co-crystallization when trying to exchange by soaking, etc. Zsolt and I
could share renin stories someday ;)
Steve
-----Original Message-----
From: CCP4 bulletin board [mailto:[log in to unmask]] On Behalf Of
Vellieux Frederic
Sent: Tuesday, June 01, 2010 6:00 AM
To: [log in to unmask]
Subject: Re: [ccp4bb] Ligand present in only one monomer in NCS
Hi Andy,
I'd say fairly common, and there can be several reasons. One is that the
entrance of the active site (in case of crystal soaks) is blocked in
some subunits. Also, different affinities in the different active sites,
plus allosteric effects, are possibilities to consider.
The latest example here I can give you (unpublished yet) is a mutant of
an NAD-binding tetrameric enzyme. The crystals were grown by
co-crystallisation. Out of the 4 active sites, only 2 of them contain
cofactor plus substrate analogue.
It is likely that the scientists who do large scale analyses of the PDB
using automated programs have done a systematic search in the PDB and
could provide you with accurate statistics. I wouldn't know any
reference to such work (I am not in that field myself).
Fred.
ANDY DODDS wrote:
> Hello,
>
> I am solving a structure of an enzyme, which crystallises as a dimer.
> We have pretty good evidence that this operates as a dimer in vitro,
> also. We have an inhibitor of this enzyme, which we are keen to
> visualise by X-ray methods.
> We seem to have very strong density in which we can model our
> inhibitor, with good stats and no negative density. However, there is
> only density in one of the monomers, nothing in the other. The SG is
> P212121, and although I can postulate why this may have happened (if
> this is indeed what HAS happened), different solvent channel
> accessibility etc., I would like to know how common this was and, if
> possible, some literature regarding this, if the board would be so
> kind?
>
>
> Regards,
>
> Andrew.
>
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