Developing predictive rules for coordination geometry from visible circular dichroism of copper(II) and nickel(II) ions in histidine and amide main‐chain complexes

Abstract

Circular dichroism (CD) spectroscopy in the visible region (vis‐CD) is a powerful technique to study metal–protein interactions. It can resolve individual d–d electronic transitions as separate bands and is particularly sensitive to the chiral environment of the transition metals. Modern quantum chemical methods enable CD spectra calculations from which, along with direct comparison with the experimental CD data, the conformations and the stereochemistry of the metal–protein complexes can be assigned. However, a clear understanding of the observed spectra and the molecular configuration is largely lacking. In this study, we compare the experimental and computed vis‐CD spectra of Cu2+‐loaded model peptides in square‐planar complexes. We find that the spectra can readily discriminate the coordination pattern of Cu2+ bound exclusively to main‐chain amides from that involving both main‐chain amides and a side‐chain (i.e. histidine side‐chain). Based on the results, we develop a set of empirical rules that relates the appearance of particular vis‐CD spectral features to the conformation of the complex. These rules can be used to gain insight into coordination geometries of other Cu2+–or Ni2+–protein complexes.

Truncated Amyloid-β(11–40/42) from Alzheimer Disease Binds Cu2+ with a Femtomolar Affinity and Influences Fiber Assembly

“…4B that the visible CD spectra are very similar. There are some minor differences in the relative intensity of the positive and negative CD bands, but in comparison to the wavelength shifts seen between HSA and its N-terminal peptide models, these are not significant enough to suggest a different binding conformation (58).…”

“…Visible CD spectra are extremely sensitive to coordination; the intensity and even sign of the CD bands will be greatly influenced by even small changes in geometry (57,58). Cu 2ϩ crosslinking between two adjacent A␤ molecules is not supported by the data.…”

Metal assisted peptide bond hydrolysis: Chemistry, biotechnology and toxicological implications

“…Such a band pattern is characteristic for square planar complexes of peptides containing the N-terminal R1a-R2a-His sequence (so-called ATCUN or NTS motif), shown in Fig. 13A [ [94][95][96][97]. By looking at the original peptide sequence, we stated that this effect could only be explained by a cleavage of either of two peptide bonds flanking the Glu residue.…”

Importance of the C-terminal histidine residues of Helicobacter pylori GroES for Toll-like receptor 4 binding and interleukin-8 cytokine production

“…To identify the histidine residues that participate in nickel ion binding and further influence TLR4 interactions and IL-8 production, we assessed the nickel ion binding abilities of histidine mutants via CD spectroscopy, measuring ellipticity at 440 nm and 538 nm that represented the d-d transition when formation of nickel-protein complex3132333435. WT protein reaction with the metal chelating agent, EDTA, was used as the reference.…”

“…In general, the nickel ion preferentially adopts planar coordination geometry31323335. The nickel ion has coordination numbers by four ligands34. It is reported that histidine, aspartate, glutamate and cysteine are the typically residues to coordinate nickel, among which, histidine is the most frequent over other amino acids59.…”