Hey, That is a good question, and there could be multiple reasons. One possibility could be the crystal contacts. I have experience with the pentameric vial surface protein (PMID: 24648448), and I could see the carbohydrate ligand only in a subset of protein chains in ASU.
Another reason could be partial occupancy especially when the affinity is low. Soaking with a higher-concentration of the ligand plus soaking for a longer duration might help. Another reason is already provided by James Krieger. So one has to employ an orthogonal assay to confirm. Kind regards, -Z Zaigham M Khan, PhD Associate Scientist Icahn School of Medicine at Mount Sinai Department of Oncological Sciences 1470 Madison Avenue New York United States On Sat, Mar 5, 2022 at 4:38 PM Krieger, James M <krieg...@pitt.edu> wrote: > Perhaps the subunits have different conformational states that are > differently able to bind the ligand. There are definitely oligomers where > the subunits do that e.g. mGluR1 binding domain dimer is usually 1 open > subunit and 1 closed in the active state without cations at the interface. > This is seen in both crystal structures of the isolated domain and FRET > studies of whole receptors in cells. > > Best wishes > James > > > On 5 Mar 2022, at 20:01, <Shymaa Damfo> <shymaa.damfo...@ucl.ac.uk> > wrote: > > > > 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://nam12.safelinks.protection.outlook.com/?url=https%3A%2F%2Fwww.jiscmail.ac.uk%2Fcgi-bin%2FWA-JISC.exe%3FSUBED1%3DCCP4BB%26A%3D1&data=04%7C01%7Ckriegerj%40PITT.EDU%7Ced7f4a91684648454d9608d9fee2f663%7C9ef9f489e0a04eeb87cc3a526112fd0d%7C1%7C0%7C637821073030033669%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C3000&sdata=cvfrwlylIMgKRx%2FqLdaPD3L1ksbjl%2B0EJJVReJHooQ8%3D&reserved=0 > > > > This message was issued to members of > https://nam12.safelinks.protection.outlook.com/?url=http%3A%2F%2Fwww.jiscmail.ac.uk%2FCCP4BB&data=04%7C01%7Ckriegerj%40PITT.EDU%7Ced7f4a91684648454d9608d9fee2f663%7C9ef9f489e0a04eeb87cc3a526112fd0d%7C1%7C0%7C637821073030033669%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C3000&sdata=u5dnPAFTmLiOMhSdvPY96T1W1hHVU4VuR6zl9CcyoU8%3D&reserved=0, > a mailing list hosted by > https://nam12.safelinks.protection.outlook.com/?url=http%3A%2F%2Fwww.jiscmail.ac.uk%2F&data=04%7C01%7Ckriegerj%40PITT.EDU%7Ced7f4a91684648454d9608d9fee2f663%7C9ef9f489e0a04eeb87cc3a526112fd0d%7C1%7C0%7C637821073030033669%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C3000&sdata=nPuFjKYokj5D0%2B8HbzJ4CmoF3I0jJyF%2Foyq9gyEcmn8%3D&reserved=0, > terms & conditions are available at > https://nam12.safelinks.protection.outlook.com/?url=https%3A%2F%2Fwww.jiscmail.ac.uk%2Fpolicyandsecurity%2F&data=04%7C01%7Ckriegerj%40PITT.EDU%7Ced7f4a91684648454d9608d9fee2f663%7C9ef9f489e0a04eeb87cc3a526112fd0d%7C1%7C0%7C637821073030033669%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C3000&sdata=i3n7vZg%2BAVSs1l5jgnx1heEPFjwnQFhuIiZ1zMe%2FCu8%3D&reserved=0 > > ######################################################################## > > 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/
