Ab Initio Coordination Chemistry for Nickel Chelation Motifs

Abstract

Chelation therapy is one of the most appreciated methods in the treatment of metal induced disease predisposition. Coordination chemistry provides a way to understand metal association in biological structures. In this work we have implemented coordination chemistry to study nickel coordination due to its high impact in industrial usage and thereby health consequences. This paper reports the analysis of nickel coordination from a large dataset of nickel bound structures and sequences. Coordination patterns predicted from the structures are reported in terms of donors, chelate length, coordination number, chelate geometry, structural fold and architecture. The analysis revealed histidine as the most favored residue in nickel coordination. The most common chelates identified were histidine based namely HHH, HDH, HEH and HH spaced at specific intervals. Though a maximum coordination number of 8 was observed, the presence of a single protein donor was noted to be mandatory in nickel coordination. The coordination pattern did not reveal any specific fold, nevertheless we report preferable residue spacing for specific structural architecture. In contrast, the analysis of nickel binding proteins from bacterial and archeal species revealed no common coordination patterns. Nickel binding sequence motifs were noted to be organism specific and protein class specific. As a result we identified about 13 signatures derived from 13 classes of nickel binding proteins. The specifications on nickel coordination presented in this paper will prove beneficial for developing better chelation strategies.

Molecular Insights of Nickel Binding to Therapeutic Antibodies as a Possible New Antibody Superantigen

“…Histidine binding of Ni 2+ ions is long-known and has been exploited in his-tag protein affinity purification (13). This also underlies the interaction of the major histocompatibility complex (MHC) with certain peptides (14,15), Hpn-like protein (16), in Fcg (17), and in TCRs of type IV contact dermatitis patients (18).…”

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

“…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. Thus, further research to investigate the other potential nickel ligands is required.…”

The Advent of Biotechnology in Resource Technology

“…However, the conserved amino acids in the nickel permease NixA of Helicobacter pylori have been described. Interestingly, next to aspartic acid, glutamic acid and histidine, which are known to be good nickelbinders [130], defined positions of serine, threonine, phenylalanine and asparagine were found to be crucial for NixA mediated uptake of nickel [131,132]. Though, these amino acids may not be directly involved in the interaction with the metal ion, but may be required for the conformation or stability of NixA.…”