Non-corrin proteins

Proline dipeptidase cleaves dipepetides where proline is adjacent to the N-terminal residue. The enzyme is a homodimer, with one Co ion tightly bound in each subunit. However, it has been shown that an additional Co11 ion must be added (per subunit) for activity. This second ion is relatively weakly bound and may be substituted by Mn11 with somewhat attenuated activity. Curiously, the active site ligands identified in metallohydrolases such as MetAP are conserved in this enzyme despite a generally low sequence similarity. 

Glucose isomerase catalyzes the conversion of D-glucose to D-fructose and has also been used extensively on an industrial scale.1184 Some, but not all, enzymes of this family require Co specifically, while others can function with other divalent ions. Environmental and health issues limit the concentrations of Co in culture media during D-fructose production and other metal ions are being sought as substitutes. Although the active site structure remains unknown, EXAFS, optical and EPR spectroscopy has suggest a low-spin divalent Co ion, bound by N and O-donors only (no S-donors). 

Apart from its natural occurrence, Co may find its way into other proteins either adventitiously or deliberately. A study was undertaken where the blood, serum, and plasma of workers occupationally exposed to Co were analyzed for the element.1189 When separated by gel electrophoresis under denaturing conditions, the Co fractions in all blood, serum, and plasma samples showed a similar protein pattern. A variety of proteins of differing size were found to bind Co in fractions collected at pFl 5, whereas only hemoglobin was found in the pH 7 fractions. The conclusions were that in vivo Co is bound to plasma proteins, perhaps albumin and hemoglobin. 

The Zn11 ion of angiotensin-converting enzyme (ACE) has been replaced by Co11 to give an active, chromophoric enzyme and inhibitor binding has been identified spectroscopically. Visible and MCD spectroscopy were used to characterize the catalytic metal binding site in the 

Co-for-Zn substitution in alcohol dehydrogenase from Saccharomyces cerevisiae revealed a 100-fold increase in activity and a higher resistance of the modified protein to the inhibitory action of other divalent transition metals,1208 making the Co-modified enzyme suitable for biotechnological applications. 

---