Density Functional Theory Analysis of Methanobactin Analog Peptides for Cu(Ii) Selectivity

Document Type


Degree Name

Master of Science (MS)



Date of Award

Summer 2013


Methanobactin (Mb) is a copper binding peptide initially identified in the methanotroph Methylococcus capsulatus and in Methylosinus trichosporium OB3b during the isolation of particulate methane monooxygenase (pMMO). OB3b is composed of 7 amino acid residues with two oxazalone rings, which take part in binding to copper ions. Mb has an extremely high affinity for binding to Cu(I) at pH 6.8. It can reduce Cu(II) to Cu(I). Mb also binds a variety of other metals such as Fe, Ni, and Zn. Zinc-fingers are short peptide sequence motifs characterized by the coordination of the Zn(II) ion, which stabilizes the finger-like folding. Zif268 binds to Zn(II) via Cys2-His2 ligation system. The metal ion binding properties of the oligopeptides acetyl-histidine-cysteine-glycine-proline-histidine-cysteine and methylbutanol-oxazolone-enethiol-glycine-proline-oxazolone-enethiol-glycine that reproduce some of the sequence properties of Mbs and Zif268 were studied using B3LYP hybrid functional and 6-311G basis set in aqueous phase. Geometry optimization and frequency calculations reveals that ac-Hisa-Cysb-Glyc-Prod-Hise-Cysf and methylbutanola- oxazolone-enethiolb-Glyc-Prod- oxazolone-enethiole-Glyf peptides bind to metal ions in the order of Fe(III) >Ni(II) > Cu(I) > Cu(II)> Zn(II)> Fe(II) in the aqueous-phase. This binding affinity order of B3LYP method was compared with the binding affinity order obtained in experimental data.


Laurence Angel

Subject Categories

Chemistry | Physical Sciences and Mathematics