Nickel-dependent enzyme

Nickel-dependent enzymes are a broad class of metalloenzymes that require nickel as a central cofactor for catalytic activity. Found in archaea, bacteria, plants, and some eukaryotes, they are grouped into redox (e.g., hydrogenase, methyl-coenzyme M reductase) and nonredox enzymes (e.g., urease, glyoxalase I)[1][3][4][6]. Their biological roles span essential cellular processes, such as hydrolysis (e.g., urease breaking down urea), redox transformations in energy metabolism (e.g., [NiFe]-hydrogenase, carbon monoxide dehydrogenase, acetyl-CoA decarbonylase/synthase), and racemization (lactate racemase)[1][3][6]. Nickel-dependent enzymes often display complex active-site architectures, sometimes incorporating nickel as part of a multinuclear metal center or in conjunction with cofactors like the nickel-pincer nucleotide[3][6]. There are at least 14 currently described nickel-dependent enzymes, mostly in prokaryotes. Their expression and activity are tightly regulated due to the potential toxicity of free nickel ions[1][3][4]. While some individual nickel-dependent enzymes (e.g., bacterial urease) are considered validated drug targets—primarily for managing pathogens—no single therapy targets the class as a whole. The entry “Nickel-dependent enzymes” is broad and describes a class/family, not a specific gene or therapeutic target, and thus is not directly suitable as a canonical therapeutic target name[1][3][4][5][6]. Key individual nickel-dependent enzymes include: Urease (hydrolyzes urea; target for anti-ulcer drugs against Helicobacter pylori), [NiFe]-hydrogenase (catalyzes hydrogen oxidation and evolution), Methyl-coenzyme M reductase (final step of methanogenesis), Glyoxalase I, Acireductone dioxygenase, Carbon monoxide dehydrogenase/Acetyl-CoA synthase, Lactate racemase. Each has unique biological relevance and, in some pathogenic cases (e.g., bacterial urease), therapeutic potential[1][2][5][6]. Summary of why "Nickel-dependent enzymes" is not a correct therapeutic target name: This term refers to a class containing many different enzymes with different biological activities and disease associations rather than a specific molecular entity or well-defined target suitable for structured data registries. Where therapeutic relevance exists, it typically refers to specific members of this class, not the whole category[1][3][4][5][6].

Other names

Nickel enzymeNickel metalloenzyme

Catalysis mediated by coordinated nickel ion(s), enabling redox activity, substrate activation, or isomerization