Nickel: Models of Protein Active Sites

During the past decade (2002–2012), the role of nickel (Ni) in biology has taken quite a turn. Prior to this period, the primary function for Ni in biology was limited to urea hydrolysis in the enzyme urease, methane production in methyl coenzyme M reductase, and the consumption of hydrogen in NiFe-hydrogenase. Owing to recent X-ray structures, Ni has now been shown to be an important cofactor in enzymes that interconvert CO2/CO (carbon monoxide dehydrogenases); enzymes that fix cell carbon in the form of acetate (acetyl coenzyme A synthases); and enzymes involved in oxygen metabolism/oxidative stress protection (nickel superoxide dismutase). In light of these new Ni-metalloenzyme structures and the need for new and cleaner energy sources, much Ni synthetic modeling work has been focused on constructing analogues of NiFe-hydrogenase, CO dehydrogenase, acetyl coenzyme A synthase, and Ni-superoxide dismutase. These synthetic biomimetics have provided new insight from structural, spectroscopic, and reactivity studies to elucidate aspects of the catalytic mechanism of the Ni sites in these enzymes. Keywords: nickel; hydrogenase; carbon monoxide dehydrogenase; acetyl coenzyme A synthase; nickel superoxide dismutase; nickel-containing metalloenzymes; model compounds; synthetic analogs; biomimetics