NADHlike

NADHlike is a protein domain identified in a variety of bacterial, archaeal, and eukaryotic proteins that participate in electron transfer processes. The domain is typically 180–220 amino acids in length and is characterized by a Rossmann-like fold that binds nicotinamide adenine dinucleotide (NADH) or related reduced flavin cofactors. Conserved sequence motifs such as the GXGXXG glycine-rich loop near the N‑terminus and a catalytic glutamate or aspartate residue are often present, allowing the domain to act as an oxidoreductase or as a redox-sensitive regulatory module.

Members of the NADHlike family have been found in dehydrogenases, oxidases, and in multi‑subunit enzymes that link metabolic pathways to cellular energy transduction. In many organisms the domain is fused to catalytic sites of larger enzymes, providing a modular way to couple NADH oxidation to downstream chemistry. In eukaryotes, NADHlike domains appear in mitochondrial proteins that regulate the electron transport chain and are implicated in the control of reactive oxygen species production.

The domain has been catalogued in protein family databases such as Pfam (PFxxxx) and InterPro, where it is grouped with other Rossmann-fold oxidoreductase domains. Structural studies using X‑ray crystallography and NMR have illustrated the close similarity of NADHlike to classic NAD(P)-binding modules, although its binding affinity and redox potential can differ significantly from canonical dehydrogenases. Researchers exploit the domain in the design of biosensors and engineered enzymes for biotechnological applications, particularly in the synthesis of chiral alcohols and in biofuel production.