Spectroscopic and Mechanistic Studies of Co(II) Phosphoesterase and Metallo-β-lactamase Biomimetics

Abstract

Cobalt is a transition metal that is less abundant in nature than most other first row transition metals [1]. However, as a cofactor for Vitamin B₁₂ it is an essential trace element for humans [2]. Cobalt is usually found to be coordinated by a corrin ligand backbone in natural systems and one of the few true organometallic compounds in nature is the Co(III)-alkyl group in Vitamin B₁₂ (the only known vitamin to contain a metal ion) [3]. A few Co(II) containing enzymes such as prolidase, nitrile hydratase, bromoperoxidase or glucose isomerase have been isolated from bacteria [2]. However, Co(II) is extensively used as spectroscopic probe for Zn(II)-containing enzyme active sites due to its unique spectroscopic and magnetic properties. Often the catalytic activity in the cobalt substituted protein is retained [4]. The active site geometry employed by Co(II) is often found to be virtually identical to the Zn(II) enzyme in crystallographic studies [4]. The most common oxidation states are Co(II) and Co(III), with the Co(II) always having unpaired electrons rendering the ion paramagnetic [1]. Octahedral or tetrahedral geometries are easily distinguished in the electronic absorption spectra, with the absorption band of the octahedral Co(II) displaying a characteristic splitting from spin-orbit coupling [5]. Structures and inhibitor/substrate interactions in Zn(II) enzymes such as carboanhydrase, carboxypeptidase A, alcohol dehydrogenase or alkaline phosphatase have been analyzed with cobalt substitution but also Cu(I)/(II) and Fe(II)/(III) enzymes have been analyzed with this method [4].