Nickel-based Enzyme Systems

Of the eight known nickel enzymes, all but glyoxylase I catalyze the use and/or production of gases central to the global carbon, nitrogen, and oxygen cycles. Nickel appears to have been selected for its plasticity in coordination and redox chemistry and is able to cycle through three redox states (1+, 2+, 3+) and to catalyze reactions spanning ∼1.5 V. This minireview focuses on the catalytic mechanisms of nickel enzymes, with an emphasis on the role(s) of the metal center. The metal centers vary from mononuclear to complex metal clusters and catalyze simple hydrolytic to multistep redox reactions.Seven of the eight known nickel enzymes (1). CODH² interconverts CO and CO₂; ACS utilizes CO; the nickel ARD produces CO; hydrogenase generates/utilizes hydrogen gas; MCR generates methane; urease produces ammonia; and SOD generates O₂.

TABLE 1

Nickel-containing enzymes

Enzyme	Reaction	Ref.
Glx I (EC 4.4.1.5)	Methylglyoxal → lactate + H2O (Reaction 1)	7
ARD (EC 1.13.11.54)	1,2-Dihydroxy-3-oxo-5-(methylthio)pent-1-ene + O2 → HCOOH + methylthiopropionate + CO (Reaction 2)	9, 10
Ni-SOD (EC 1.15.1.1)	2H+ + 2O2−̇ → H2O2 + O2 (Reaction 3)	16, 19
Urease (EC 3.5.1.5)	H2N-CO-NH2 + 2H2O → 2NH3 + H2CO3 (Reaction 4)	22, 23
Hydrogenase (EC 1.12.X.X)	2H+ + 2e− ⇌ H2 (ΔE0′ = −414 mV) (Reaction 5)	25, 26
MCR (EC 2.8.4.1)	CH3-CoM + CoBSH → CH4 + CoM-SS-CoB (Reaction 6)	42, 43
CODH (EC 1.2.99.2)	2e− + 2H+ + CO2 ⇌ CO + H2O (E0′ = −558 mV) (Reaction 7)	30, 31
ACS (EC 2.3.1.169)	CH3-CFeSP + CoASH + CO → CH3-CO-SCoA + CFeSP (Reaction 8)	30, 31

Open in a separate windowThe nickel sites in enzymes exhibit extreme plasticity in nickel coordination and redox chemistry. The metal center in SOD must be able to redox processes with potentials that span from +890 to −160 mV (2), whereas in MCR and CODH, it must be able to reach potentials as low as −600 mV (3); thus, nickel centers in proteins perform redox chemistry over a potential range of ∼1.5 V!Because natural environments contain only trace amounts of soluble Ni²⁺, attaining sufficiently high intracellular nickel concentrations to meet the demand of the nickel enzymes requires a high affinity nickel uptake system(s) (4), molecular and metallochaperones (5), and sensors and regulators of the levels of enzymes involved in nickel homeostasis (6). However, space limitations prevent coverage of these pre-catalytic events.