CHAPTER 14: Cobalt and Nickel

Cobalt and nickel play key roles in biological systems as cofactors in a small number of important enzymes. The majority of these are found in microbes. Evidence for direct roles for Ni(II) and Co(II) enzymes in higher organisms is limited, with the exception of the well-known requirement for the cobalt-containing vitamin B₁₂ cofactor and the Ni-dependent urease in plants. Nonetheless, nickel in particular plays a key role in human health because of its essential role in microbes that inhabit various growth niches within the body. These roles can be beneficial, as can be seen with the anaerobic production and consumption of H₂ in the digestive tract by bacteria and archaea that results in increased yields of short-chain fatty acids. In other cases, nickel has an established role in the establishment of pathogenic infection (Helicobacter pylori urease and colonization of the stomach). The synthesis of Co- and Ni-containing enzymes requires metal import from the extracellular milieu followed by the targeting of these metals to the appropriate protein and enzymes involved in metallocluster or cofactor biosynthesis. These metals are toxic in excess so their levels must be regulated carefully. This complex pathway of metalloenzyme synthesis and intracellular homeostasis requires proteins that can specifically recognize these metals in a hierarchical manner. This chapter focuses on quantitative and structural details of the cobalt and nickel binding sites in transport, trafficking and regulatory proteins involved in cobalt and nickel metabolism in microbes.