cupin

Cupin is a large and diverse protein superfamily defined by a conserved β-barrel fold and two short conserved sequence motifs. Members include enzymes with metal-dependent catalytic activities and storage proteins found in plants, fungi, bacteria, and some animals. The name derives from the cupin motifs that characterize the fold. Cupins are categorized as monocupins (single cupin domain) or bicupins (two cupin domains in tandem).

Structural features: Cupins fold into a jelly-roll beta-barrel built from duplication of a conserved motif. The two motifs typically harbor histidine and glutamate residues that coordinate metal ions such as Mn2+, Fe2+, or Cu2+ required for catalysis in many family members. The metal center plus neighboring residues enable diverse chemistries, including dioxygenases, isomerases, hydrolases, and epimerases. Some cupins function without metal cofactors.

Functions and examples: Plant seed storage proteins such as vicilins and legumins are cupins. Germin-like proteins (GLPs) form a plant defense-related group and often have oxalate oxidase activity or other oxidoreductase functions. Other cupins include quercetin dioxygenase and various bacterial and fungal enzymes involved in metabolism, detoxification, and nutrient cycling.

Distribution and evolution: Cupins are widespread in bacteria, fungi, plants, and some animals. They are ancient and have diversified through gene duplication and domain rearrangements, producing monocupin and bicupin architectures and a wide range of biochemical functions. The cupin superfamily continues to be a focal point in studies of protein structure–function relationships and metal-dependent catalysis.