Dear all, I don't think, there is much to add to the statement of Bernhard or James that different protomers in the asymmetric unit (must) have some difference in there contacts and therefore often in their conformation. What it doesn't answer is a chicken or the egg question:
do the different environments in the crystal allow or force different conformations (e.g. open or closed loops) and/or different (active) site occupancies or do different states in an oligomer allow or force crystallization only in a packing and space group with multiple states? Latter could be due to an anti-cooperative binding to a dimer. We have seen this in the dimeric Tet repressor: wt binds the ligand (a tetracycline) in each monomer of the dimer with one chain in the asymmetric unit, but some of the mutants bind only one ligand per dimer (confirmed by ITC, Biochimica et Biophysica Acta, 2020). Despite the same packing, this forces reduction of space group symmetry from I422 to P422 (omitting screws). >From the crystal structures alone, I think, one cannot prove what comes first. From my gut feeling, in most cases multiple states in solution force multiple states in the crystal - in other words - I tend to say, multiple states in the crystal are "real" in the sense they also occur in solution. Does somebody want to comment on this? Greetings Gottfried Am Sonntag, den 06-03-2022 um 00:40 schrieb Bernhard Rupp: As you stated, you have multiple protomers in the asymmetric unit, where they are free from crystallographic symmetry constraints. Generally that means different local environment for each protomer. Inspecting the sites in the different protomers (frequently related by various non-crystallographic symmetry operations) often can reveal plausible reasons for different occupancies. One hydrogen bond more or less for example can mean a difference of 4 orders of magnitude in Kd. Best, BR -----Original Message----- From: CCP4 bulletin board On Behalf Of Sent: Saturday, March 5, 2022 12:01 To: CCP4BB@JISCMAIL.AC.UK Subject: [ccp4bb] ligand binds to one molecule Hello all, In homo-dimeric or homo-oligomeric protein crystal structures, what would be the reason for having a ligand (chemical compound or fragment) binds to one molecule and not all molecules in the asymmetric unit? I have soaked a fragment that has an affinity of 200 uM to a viral protein but I can only see it binds to one molecule (we have eight molecules in the AU). This is was also notable as well in some published PDB (dimeric protein). Any suggestions? Best wishes, Shymaa ######################################################################## To unsubscribe from the CCP4BB list, click the following link: https://www.jiscmail.ac.uk/cgi-bin/WA-JISC.exe?SUBED1=CCP4BB&A=1 This message was issued to members of www.jiscmail.ac.uk/CCP4BB, a mailing list hosted by www.jiscmail.ac.uk, terms & conditions are available at https://www.jiscmail.ac.uk/policyandsecurity/ ######################################################################## To unsubscribe from the CCP4BB list, click the following link: https://www.jiscmail.ac.uk/cgi-bin/WA-JISC.exe?SUBED1=CCP4BB&A=1 This message was issued to members of www.jiscmail.ac.uk/CCP4BB, a mailing list hosted by www.jiscmail.ac.uk, terms & conditions are available at https://www.jiscmail.ac.uk/policyandsecurity/ ######################################################################## To unsubscribe from the CCP4BB list, click the following link: https://www.jiscmail.ac.uk/cgi-bin/WA-JISC.exe?SUBED1=CCP4BB&A=1 This message was issued to members of www.jiscmail.ac.uk/CCP4BB, a mailing list hosted by www.jiscmail.ac.uk, terms & conditions are available at https://www.jiscmail.ac.uk/policyandsecurity/
