Active Site

Pyridine nucleotide-disulphide oxidoreductase, class-II, active site (IPR008255)

Short name: Pyr_nucl-diS_OxRdtase_2_AS


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 [PMID: 2067578], PNDR can be categorised into 2 groups.

Class II includes: prokaryotic and eukaryotic thioredoxin reductases [PMID: 3288628, PMID: 8106340]; bacterial alkyl hydroperoxide reductases [PMID: 2191951]; bacterial NADH:dehydrogenases [PMID: 1917890]; a probable oxidoreductase encoded in the Clostridium pasteurianum rubredoxin operon [PMID: 1637309]; and yeast hypothetical protein YHR106w.

The 3D structure of Escherichia coli thioredoxin reductase (TR) has been solved [PMID: 2067578, PMID: 8114095]. The protein exists as a homodimer, with 3 domains per monomer, which correspond to the FAD-binding, NAD(P)H-binding and central domains of glutathione reductase (GR) (cf. signature PNDRDTASEI). However, TR lacks the domain that provides the dimer interface in GR, and forms a completely different dimeric structure. The relative orientation of these domains is very different in the 2 enzymes: when the FAD-binding domains of TR and GR are superimposed, the NADPH-binding domain of one is rotated by 66 degrees with respect to the other. The FAD- and NAD(P)H-binding domains have a similar doubly-wound alpha/beta fold, suggesting they evolved by gene duplication [PMID: 1995341]. While in GR the redox active disulphide is located in the FAD-binding domain, in TR it lies in the NADPH-binding domain. This suggests that the enzymes diverged from an ancestral nucleotide-binding protein and acquired their disulphide reductase activities independently [PMID: 2067578].

The sequence around the two cysteines involved in the redox-active disulphide bond is conserved, and is covered by this pattern.

GO terms

Biological Process

GO:0055114 oxidation-reduction process

Molecular Function

GO:0016491 oxidoreductase activity

Cellular Component

No terms assigned in this category.

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.
PROSITE patterns