Hi Tristan et al, before people invest their time into re-refining a model against the deposited data, I'd suggest that these data are dubious - see table S3 in https://pubs.acs.org/doi/suppl/10.1021/jacs.9b02505/suppl_file/ja9b02505_si_001.pdf ! The data processing statistics look "surprising" to me: "Rsym or Rmerge" values are unexpectedly high, and the high-resolution cutoffs for 2 of the 3 structures are too low. Maybe the space group is wrong? With such data, ligand density cannot expected to be meaningful, I'd say. In my eyes, the authors should be asked for the raw data images, and these should be reprocessed before re-refinement.
best, Kay On Fri, 19 Jul 2019 17:05:21 +0100, Tristan Croll <[email protected]> wrote: >I couldn't resist doing a little playing with 6mo0 in ISOLDE. The >sequence past Gly1151 is wrong - after jumping a small gap (density >clearly indicates a single missing residue here), it continues on from >1165. Corrected the following sequence to GVVTRS, deleted the ligands, >did some basic energy minimisation and cleaning up of obvious local >problems, reset the B-factors and refined in Phenix.refine. Rwork/Rfree >28/32, MolProbity score 2.14 (vs. 3.6 originally). No sign of anything >like the ligand in the difference density (just a small blob in the >active site). Some other oddities make me suspect a number of point >mutations from the assigned sequence (not register errors - the >surrounds are quite clear). I'm particularly intrigued by residues 48-71 >- this stretch appears to link seamlessly head-to-tail with its own >symmetry copy, forming a seemingly-continuous chain snaking through the >crystal. Can't make head nor tail of that. A decidedly odd structure... >but I agree with you that the ligand doesn't seem supported by the >density. > >Best regards, > >Tristan > >On 2019-07-19 14:46, [email protected] wrote: >> Hi Rhys, >> >> There is definitively some density present for a ligand, but the >> active site region looks completely misfitted, and the ligand density >> may also belong to unfitted protein residues. One first needs to get >> the protein chain right, and should then look if there would still be >> density available to fit the ligand. >> >> Best, >> >> Herman >> >> VON: CCP4 bulletin board [mailto:[email protected]] IM AUFTRAG VON >> Rhys Grinter >> GESENDET: Freitag, 19. Juli 2019 15:22 >> AN: [email protected] >> BETREFF: [EXTERNAL] [ccp4bb] Questionable Ligand Density: 6MO0, 6MO1, >> 6MO2 >> >> EXTERNAL : Real sender is [email protected] >> >> Hi All, >> >> I was chatting with a colleague during a recent synchrotron visit and >> they'd recently come across some ligand/drug bound structures >> associated with a paper recently published in a high impact factor >> journal. >> >> They had pulled the associated SFs from the PDB and found that the >> electron density associated with these ligands didn't match that >> reported in the paper and certainly wasn't sufficient to model the >> alleged ligand. >> >> I also pulled the structure factors and after refinement in the >> presence/absence of the alleged ligand I also feel that the density >> present does not warrant modelling of the ligand. >> >> I was hoping that the community might be able to give me an outside >> opinion on these datasets (PDB IDs: 6MO0, 6MO1, 6MO2) and if the >> problem associated with the data is verified, provide some advice on >> how to proceed. >> >> This isn't the first occasion I've seen ligand bound structures with >> questionable density deposited in association with papers in well >> respected journals. Despite improvements to validation I feel that >> this problem is widespread. >> >> Best Regards, >> >> Rhys >> >> -- >> >> Dr Rhys Grinter >> >> NHMRC Postdoctoral Researcher >> >> Monash University >> >> +61 (0)3 9902 9213 >> >> +61 (0)403 896 767 >> >> ------------------------- >> >> To unsubscribe from the CCP4BB list, click the following link: >> https://www.jiscmail.ac.uk/cgi-bin/webadmin?SUBED1=CCP4BB&A=1 [1] >> >> ------------------------- >> >> To unsubscribe from the CCP4BB list, click the following link: >> https://www.jiscmail.ac.uk/cgi-bin/webadmin?SUBED1=CCP4BB&A=1 [2] >> >> Links: >> ------ >> [1] >> https://urldefense.proofpoint.com/v2/url?u=https-3A__www.jiscmail.ac.uk_cgi-2Dbin_webadmin-3FSUBED1-3DCCP4BB-26A-3D1&d=DwMFaQ&c=Dbf9zoswcQ-CRvvI7VX5j3HvibIuT3ZiarcKl5qtMPo&r=HK-CY_tL8CLLA93vdywyu3qI70R4H8oHzZyRHMQu1AQ&m=KR65gleAznAqJKiHPp9vvVZeSsv8LHvr5PDyckgEaWw&s=NmR2g-LBQtuhDFsFRJPffbzIm3cQQWMhK7ozfrse7KY&e= >> [2] https://www.jiscmail.ac.uk/cgi-bin/webadmin?SUBED1=CCP4BB&A=1 > >######################################################################## > >To unsubscribe from the CCP4BB list, click the following link: >https://www.jiscmail.ac.uk/cgi-bin/webadmin?SUBED1=CCP4BB&A=1 ######################################################################## To unsubscribe from the CCP4BB list, click the following link: https://www.jiscmail.ac.uk/cgi-bin/webadmin?SUBED1=CCP4BB&A=1
