Rossmanntype

Rossmann-type, commonly referred to as the Rossmann fold, is a widespread protein structural motif that forms the core of many dinucleotide-binding enzymes. It is named after Michael Rossmann, who described recurring nucleotide-binding patterns in NAD-binding proteins.

The structure consists of a curved, mostly parallel beta-sheet flanked by alpha helices on both sides, arranged in a βαβ motif that repeats along the chain to create a compact dinucleotide-binding domain. A conserved phosphate-binding loop, often glycine-rich, lies between the first beta strand and the first alpha helix and interacts with the phosphate groups of NAD(), NADP(), or FAD. This arrangement creates a binding site that accommodates dinucleotide cofactors in a way that supports redox chemistry.

Functionally, the Rossmann-type fold provides a stable platform for binding nicotinamide- or flavin-containing cofactors and positioning them for hydride transfer or electron transfer during catalysis. As a result, it is a common feature of many oxidoreductases and dehydrogenases, including well-known enzymes such as glyceraldehyde-3-phosphate dehydrogenase and malate dehydrogenase, among numerous others across bacteria, archaea, and eukaryotes.

Variations of the motif exist, with differences in loop regions that influence cofactor and substrate specificity. While the Rossmann fold denotes a particular tertiary structure, the broader term “Rossmann-type” can refer to related dinucleotide-binding domains that share the characteristic βαβ architecture.

See also: Rossmann fold, dinucleotide-binding motif, NAD-binding, FAD-binding, dehydrogenase.