Cisplatin coordination chemistry determination at hen egg white lysozyme His15 with ligand distances and angles, and their standard uncertainties, and also reporting a split occupancy effect

Abstract

Following the interest of L Messori and A Merlino 2016 Coordination Chemistry Reviews (2016, 315, in the platinum ions' coordination geometries in our PDB entries 4dd4 and 4dd6 we have extended our analyses to find out if the precise geometric details they seek, with distance and angle standard uncertainties, are possible. For the case of 4dd4 it has proved possible and whereby we made a comparison of with-ligand-restraints and without-ligand-restraints models, and derived the standard uncertainties for the latter using the Diffraction Precision Index ('DPI')method. This proved not to be possible for 4dd6-new however due to a split occupancy effect on the bound cisplatin, and whose chemical identity is not certain. It is very interesting what they are though, and for which attention has also been drawn to such an effect in the studies reported by Ferraro et al 2016. We plan then an extensive reanalysis of all the existing datasets of cisplatin bound to histidine with a detailed look for such split occupancy effects, which we will now undertake and report later in the rather new 'data review' style of article. All these extended analyses, reported here and that we plan in our data review, are outside the scope of our original paper (Tanley et al 2012) and whose conclusions are obviously not affected, namely that DMSO is important for cisplatin binding to histidine versus under aqueous conditions. Such new and extended analyses, based on improved crystal structure analysis tools and/or more recent structural insights, are likely to be increasingly important in macromolecular crystallography and are within the vision of the 'Living PDB and Living Publication' (espoused by Helliwell, Terwilliger and McMahon (2012). SummaryWe have extended our previously published crystal structure refinements of cisplatin binding to hen egg lysozyme using the existing diffraction data for our PDB entries 4dd4 and 4dd6 (Tanley et al 2012). This follows the interest of Messori and Merlino 2016 in the platinum ions' precise coordination geometry. Figure 1.It was not possible to extend the diffraction data resolution limit via a re-processing of 4dd4 or 4dd6 diffraction data, which is limited simply by the geometry of the measuring protocol used. The diffraction data sets were processed using EVAL15 (Schreurs et al., 2010) as previously described in Tanley et al 2012.The focus of our first paper Tanley et al 2012 was on the platinum ion occupancies as a function of use of DMSO or not, and whose observations are entirely consistent with these two improved model refinements. As noted in detail in Tanley et al 2012 the anomalous difference peaks on the platinum atoms are highly significant (above 25 sigma in each case, see Figure 1). The PDB depositions for 4dd4-new and 4dd6-new are now replaced by new PDB depositions with codes:-5L3H and 5L3I.Overall, the coordination geometry that each Pt δ shows in 4dd4-new and 4dd6-new, for the Table S1 provides a summary of the diffraction data, which are unchanged obviously but repeated he...

A Combined Spectroscopic and Protein Crystallography Study Reveals Protein Interactions of RhI(NHC) Complexes at the Molecular Level

“…This interaction was concomitant to the loss of p -cymene and coordination of arginine (Arg)­14. , Over a longer period of time, a secondary interaction with lysine (Lys)­33 of HEWL was found . Lys33 has been suggested as a potential site for interaction with platinum complexes. , …”

“…46 Lys33 has been suggested as a potential site for interaction with platinum complexes. 47,48 In order to add to the understanding of the behavior of M(NHC) complexes in biological environments, we herein report investigations on the hydrolytic stability of a [RhCl-(COD)(NHC)] complex and a peptide-coordinated analogue. Furthermore, a protein crystallographic study sheds light on the way the hydrolytic stability of the complexes is related to their interactions with HEWL.…”