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, herman.schreu...@sanofi.com 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:CCP4BB@JISCMAIL.AC.UK] IM AUFTRAG VON
Rhys Grinter
GESENDET: Freitag, 19. Juli 2019 15:22
AN: CCP4BB@JISCMAIL.AC.UK
BETREFF: [EXTERNAL] [ccp4bb] Questionable Ligand Density: 6MO0, 6MO1,
6MO2
EXTERNAL : Real sender is owner-ccp...@jiscmail.ac.uk
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
