Characterization of Chromodulin by X-ray Absorption and Electron Paramagnetic Resonance Spectroscopies and Magnetic Susceptibility Measurements

Abstract

The biologically active form of the essential trace element chromium is believed to be the oligopeptide chromodulin. Chromodulin binds four chromic ions before binding at or near the active site of activating insulin receptor and subsequently potentiating the tyrosine kinase activity of the receptor. Charge balance arguments and preliminary spectroscopic studies suggested that the chromic centers might be part of a multinuclear assembly. Using a combination of X-ray absorption and electron paramagnetic resonance spectroscopies and variable-temperature magnetic susceptibility measurements, we found that holochromodulin is shown to possess an antiferromagnetically coupled trinuclear assembly which probably weakly interacts with a fourth chromium center. The chromium centers possess octahedron coordination comprised of oxygen-based ligation, presumably derived primarily from oligopeptide-supplied carboxylate groups. X-ray absorption data cannot be reproduced with the presence of sulfur atom(s), indicating that the cysteine thiolate group does not coordinate to the chromium centers. Thus, chromodulin possesses a unique type of multinuclear assembly, distinct from those known in other bioinorganic systems.

Breakdown kinetics of the tri-chromium(III) oxo acetate cluster ([Cr3O(OAc)6]+) with some ligands of biological interest

“…It appears that a trinuclear Cr(III)-oxo core {Cr 3 O} in a peptidic environment may be a significant biological form of Cr(III) [4][5][6]. Recently, we reported on the discovery of a potential binding site for Cr(III) in the insulin receptor, and a model for the transport and activity of Cr(III)-oxo clusters in the serum [4].…”

Unusual reactivity in a commercial chromium supplement compared to baseline DNA cleavage with synthetic chromium complexes

“…Finally, reactions were conducted with Cr(succinate) and Cr(N-acetyl-L L-glutamate), and the amino acid complex, [Cr(His) 2 ]. The diacid complexes of malonate, succinate and N-acetyl-L L-glutamate are used here are carboxylate-rich models for the ''low molecular weight binding substance'' described by Vincent and coworkers [23,40]. The last three complexes showed only low levels of activity and only at the highest metal concentrations.…”

Isolation of a novel chromium(III) binding protein from bovine liver tissue after chromium(VI) exposure

“…There have been ample attempts to elucidate the amino acid sequence of chromium(III) binding proteins/peptides, but to date they have been unsuccessful for reasons that remain unclear [8,29]. Information regarding the secondary, tertiary and quaternary structure of this molecule could not be determined from the experiments presented here but hopefully will become available in future studies.…”

“…These chromium(III) ions result from the reduction of chromium(VI). Evidence indicates that three of the four chromium(III) ions are part of a trinuclear assembly and are antiferromagnetically coupled [8]. In addition, there is evidence that this cluster might electronically interact with a fourth chromium center [8].…”

“…Evidence indicates that three of the four chromium(III) ions are part of a trinuclear assembly and are antiferromagnetically coupled [8]. In addition, there is evidence that this cluster might electronically interact with a fourth chromium center [8]. However, in each of these accounts no evidence was presented that these studies were performed on the pure peptide.…”