Hello, could this be a case of the ZN not being shifted one place to the left 
in the PDB file to give it the right scattering factor ? ? The progs are 
pushing neighbouring atoms into the Zn density to account for its scattering 
power ? ? Maybe these problems don't happen any more.

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-------- Original Message --------
On 11 Apr 2022, 15:55, Martin Moche wrote:

> Dear colleagues,
>
> We are refining a structure where an acetate ion (ACT) binds a zinc ion, Zn+2 
> (ZN), using an excellent quality 1.38Å dataset, however the acetate oxygen 
> ends up too close (1.2Å) to the ZN during restrained refinement in refmac5? 
> Moreover, the ACT ion gets “deformed” so that the acetate oxygen-carbon bond 
> gets extended into 1.4Å?
>
> When doing COOT sphere refinement, the acetate ion moves on top of the ZN? 
> like the ZN was not there? And we think this would happen also in refmac5, if 
> the electron density were not holding acetate ion back from entering the zinc 
> site. We guess on a “tug of war” between ZN site attraction for acetate 
> oxygen, and electron density for other three acetate atoms, is deforming the 
> acetate ion. Why is the acetate ion not aware of the ZN in COOT? and refmac5…
>
> In the attached image, we removed the deformed acetate ion from refinement 
> resulting in the green difference density contoured at 5σ. The deformed 
> acetate from previous refinements (gold color carbons) has a carbon-oxygen 
> bond of 1.4Å and an oxygen-zinc distance of 1.2Å. The oxygen-zinc distance is 
> typically around 1.8Å for previous acetate ions (magenta carbons) modeled in 
> other PDB entries of the same enzyme.
>
> To get more reasonable refinement we manually attempted to add LINK (and 
> LINKR) restraints in the PDB file for the oxygen-zinc bond but that had no 
> impact on refmac5 and COOT refinement? although notified in the refmac5 
> logfiles (attached).
>
> COOT is intended to parse LINK records and are not using nonbonded restraints 
> (1). We share our LINK records here for review.
>
> LINK ZN ZN A 625 OE1 GLU A 318 1555 1555 2.060
>
> LINK ZN ZN A 625 OE2 GLU A 318 1555 1555 2.060
>
> LINK O ACT A 623 ZN ZN A 625 1555 1555 2.060
>
> LINKR O ACT A 623 ZN ZN A 625 1555 1555ACT-ZN
>
> LINKR ZN ZN A 625 NE2 HIS A 299 ZN-HISNE
>
> LINKR ZN ZN A 625 NE2 HIS A 295 ZN-HISNE
>
> We tried with one LINK or LINKR row or with both present in PDB (as above) 
> and used various checkboxes under “Advanced options” (pictured) under 
> Refinement-Refmac5 > Inputs > Restraints
>
> Metal coordination vary with oxidation state and despite AceDRG (2) and 
> recent CCP4 developments (3) we are now struggling with Zinc and acetate ion 
> in our refinement.
>
> Maybe we have run into a BUG? or how should we proceed?
>
> Best regards,
>
> Martin
>
> P.S.
>
> Also, in phenix.refine the acetate ion moves too close to the ZN? And one if 
> the zinc coordinated water molecules left its electron density and moved 
> towards the ZN..?
>
> D.S.
>
> 1. Casanal A, Lohkamp B, Emsley P. Current developments in Coot for 
> macromolecular model building of Electron Cryo-microscopy and 
> Crystallographic Data. Protein Sci. 2020;29(4):1069-78.doi:10.1002/pro.3791.
>
> 2. Nicholls RA, Joosten RP, Long F, Wojdyr M, Lebedev A, Krissinel E, 
> Catapano L, Fischer M, Emsley P, Murshudov GN. Modelling covalent linkages in 
> CCP4. Acta Crystallogr D Struct Biol. 2021;77(Pt 
> 6):712-26.doi:10.1107/S2059798321001753.
>
> 3. Nicholls RA, Wojdyr M, Joosten RP, Catapano L, Long F, Fischer M, Emsley 
> P, Murshudov GN. The missing link: covalent linkages in structural models. 
> Acta Crystallogr D Struct Biol. 2021;77(Pt 
> 6):727-45.doi:10.1107/S2059798321003934.
>
> [Head of Macromolecular X-ray Crystallography](https://ki.se/en/mbb/psf-mx) | 
> [Protein Science Facility](https://ki.se/en/mbb/protein-science-facility)
>
> [Medical Biochemistry and 
> Biophysics](https://ki.se/en/mbb/department-of-medical-biochemistry-and-biophysics)
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