InterPro domain: IPR001100

The pyridine nucleotide-disulphide reductases (PNDR) use the isoalloxazine ring of FAD to shuttle reducing equivalents from NAD(P)H to a Cys residue that is usually a part of a redox-active disulphide bridge. In a second step, the reduced disulphide reduces the substrate. On the basis of sequence and structural similarities [ 1 ], PNDR can be categorised into 2 groups.

Class I includes glutathione reductase, trypanothione reductase, lipoamide dehydrogenase and mercuric reductase. They cover a wide range of catalytic functions: glutathione reductase ensures that the cell has enough reduced glutathione to maintain protein thiol groups in the reduced state [ 2 ]; trypanothione reductase carries out the analogous reaction in trypanosomal cells (trypanothione is an analogue of glutathione) [ 3 ]; lipoamide dehydrogenase, the E3 component of alpha-ketoacid dehydrogenase multienzyme complex, oxidises the dihydrolypoyl groups of lipoate acyltransferase, and so couples glycolysis to the tricarboxylic acid cycle [ 4 ]; and mercuric reductase enables bacteria to detoxify the mercuric ion by reducing it to elemental mercury, which evaporates from the cell [ 5 ].

1. Convergent evolution of similar function in two structurally divergent enzymes. Nature 352, 172-4
2. Variations in the activity of glutathione reductase and the cellular glutathione content in relation to sensitivity to methylviologen in Escherichia coli. Arch. Biochem. Biophys. 282, 233-8
3. Purification and characterization of trypanothione reductase from Crithidia fasciculata, a newly discovered member of the family of disulfide-containing flavoprotein reductases. Biochemistry 25, 3519-26
4. Dihydrolipoamide dehydrogenase: functional similarities and divergent evolution of the pyridine nucleotide-disulfide oxidoreductases. Arch. Biochem. Biophys. 268, 409-25
5. Bacterial resistances to inorganic mercury salts and organomercurials. Plasmid 27, 4-16