Hi,

A few weeks ago, I have already cited renin as such an example. With two slightly differerent molecules in the asu, certain inhibitors bind only to one of them and the other renin molecule is empty.
Look at 2G24 for example in the PDB.
Molecule A is loaded, while B is empty. The difference in binding is certainly due to small conformational differences between the two independent molecules in the asu.
In most of the other structuers with other chemotypes both sites could be loaded.
In further examples (3KM4) crystal contacts create additional, probably weak binding sites (4 inhibitors bound to two renin molecules in the asu).
And this is not all. As Steve Soisson pointed out last time, many stories could be shared on this.

regards,

Zsolt Bocskei
sanofi-aventis
Strasbourg

2010/6/21 FREITAG-POHL S. <[log in to unmask]>

Dear all,

I am wondering if there are publications, where it is shown
that a ligand/substrate was not able to bind in one crystal
form of a protein, but was found in another crystal form.
In other words:
is there a case where the crystal packing interactions are
proofed to be responsible for non-binding of a substrate?

Thanks for any hints,

Stefanie

Dr. Stefanie Freitag-Pohl
Durham University
Chemistry Dept
South Road
Durham. DH1 3LE
Tel: 0191 3342143
Email: [log in to unmask]