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:ccp...@jiscmail.ac.uk] On Behalf Of Vellieux Frederic Sent: Tuesday, June 01, 2010 6:00 AM To: CCP4BB@JISCMAIL.AC.UK 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 The latest example here I can give you (unpublished yet) is a mutant of an NAD-binding tetrameric enzyme.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. > Notice: This e-mail message, together with any attachments, contains information of Merck & Co., Inc. (One Merck Drive, Whitehouse Station, New Jersey, USA 08889), and/or its affiliates Direct contact information for affiliates is available at http://www.merck.com/contact/contacts.html) that may be confidential, proprietary copyrighted and/or legally privileged. It is intended solely for the use of the individual or entity named on this message. If you are not the intended recipient, and have received this message in error, please notify us immediately by reply e-mail and then delete it from your system.
