Pathways & interactions
Pyridine nucleotide-disulphide oxidoreductase, class-II (IPR000103)
Short name: Pyridine_nuc-diS_OxRdtase_2
Overlapping homologous superfamilies
- FAD/NAD(P)-binding domain superfamily (IPR036188)
- Pyridine nucleotide-disulphide oxidoreductase, class-II (IPR000103)
- Alkyl hydroperoxide reductase F subunit homogue, putative (IPR017561)
- Alkyl hydroperoxide reductase subunit F (IPR012081)
- Bacillithiol biosynthesis thiol disulphide oxidoreductase, YpdA (IPR023856)
- Ferredoxin--NADP reductase, type 2 (IPR022890)
- Thioredoxin reductase (IPR005982)
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 metal reductase from Desulfotomaculum reducens which reduces Fe(III)-chelates to Fe(II)-chelates [PMID: 25389064]; 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].
- PR00469 (PNDRDTASEII)