An informatics search for the low-molecular weight chromium-binding peptide

Deendayal Dinakarpandian¹ , Vincent Morrissette² , Shveta Chaudhary² , Kambiz Amini² , Brian Bennett³ and J David Van Horn²

¹Division of Computer Science and Electrical Engineering, School of Computing and Engineering, University of Missouri-Kansas City, Kansas City, MO 64110, USA

²Department of Chemistry, University of Missouri-Kansas City, 5110 Rockhill Road, Kansas City, MO 64110, USA

³National Biomedical EPR Center, Medical College of Wisconsin, Milwaukee, WI 53226 USA

author email corresponding author email

BMC Chemical Biology 2004, 4:2doi:10.1186/1472-6769-4-2


Published:	16 December 2004

Abstract

Background

The amino acid composition of a low molecular weight chromium binding peptide (LMWCr), isolated from bovine liver, is reportedly E:G:C:D::4:2:2:2, though its sequence has not been discovered. There is some controversy surrounding the exact biochemical forms and the action of Cr(III) in biological systems; the topic has been the subject of many experimental reports and continues to be investigated. Clarification of Cr-protein interactions will further understanding Cr(III) biochemistry and provide a basis for novel therapies based on metallocomplexes or small molecules.

Results

A genomic search of the non-redundant database for all possible decapeptides of the reported composition yields three exact matches, EDGEECDCGE, DGEECDCGEE and CEGGCEEDDE. The first two sequences are found in ADAM 19 (A Disintegrin and Metalloproteinase domain 19) proteins in man and mouse; the last is found in a protein kinase in rice (Oryza sativa). A broader search for pentameric sequences (and assuming a disulfide dimer) corresponding to the stoichiometric ratio E:D:G:C::2:1:1:1, within the set of human proteins and the set of proteins in, or related to, the insulin signaling pathway, yields a match at an acidic region in the α-subunit of the insulin receptor (-EECGD-, residues 175–184). A synthetic peptide derived from this sequence binds chromium(III) and forms a metal-peptide complex that has properties matching those reported for isolated LMWCr and Cr(III)-containing peptide fractions.

Conclusion

The search for an acidic decameric sequence indicates that LMWCr may not be a contiguous sequence. The identification of a distinct pentameric sequence in a significant insulin-signaling pathway protein suggests a possible identity for the LMWCr peptide. This identification clarifies directions for further investigation of LMWCr peptide fractions, chromium bio-coordination chemistry and a possible role in the insulin signaling pathway. Implications for models of chromium action in the insulin-signaling pathway are discussed.