Rossmannlike

Rossmannlike refers to protein domains that adopt the Rossmann fold, a common structural motif used for binding dinucleotides such as NAD+, NADP+, or FAD. The term is applied to variants that preserve the core topology but may differ in strand order or insertions, so they are described as Rossmann-like rather than strictly canonical Rossmann folds. The hallmark is a parallel beta-sheet of typically six strands flanked by alpha helices, creating a conserved dinucleotide-binding pocket.

A characteristic feature is a glycine-rich phosphate-binding loop near the N-terminus of the first beta strand, often described by motifs such as GxGGxxG. This loop coordinates the phosphate groups of bound cofactors and helps position the nicotinamide or flavin moieties for catalysis. The overall topology is versatile, supporting a range of catalytic functions beyond simple cofactor binding.

Functionally, Rossmann-like domains are common in enzymes that perform oxidation-reduction reactions. They appear in NAD-dependent dehydrogenases, oxidases, and reductases, as well as enzymes that bind other nucleotides. Classic examples include glyceraldehyde-3-phosphate dehydrogenase and lactate dehydrogenase, which illustrate the archetypal NAD-binding Rossmann-like architecture. The fold also appears in non-redox enzymes that utilize nucleotide cofactors or nucleotide-derived substrates.

Classification and distribution: Rossmann-like domains are part of the broader Rossmann superfamily and are widely distributed across bacteria, archaea, and eukaryotes. Structural classifications such as SCOP and CATH recognize variants within this family, reflecting diversity in strand arrangement and insertions while preserving the shared dinucleotide-binding core.

In research, recognizing Rossmann-like topology aids in function prediction, evolutionary studies, and rational design of inhibitors targeting cofactor binding sites.