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 [<cite idref="PUB00004100"/>], PNDR can be categorised into 2 groups.<p>Class II includes: prokaryotic and eukaryotic thioredoxin reductases [<cite idref="PUB00002489"/>, <cite idref="PUB00002259"/>]; bacterial alkyl hydroperoxide reductases [<cite idref="PUB00002553"/>]; bacterial NADH:dehydrogenases [<cite idref="PUB00002349"/>]; a probable oxidoreductase encoded in the <taxon tax_id="1501">Clostridium pasteurianum</taxon> rubredoxin operon [<cite idref="PUB00000510"/>]; and yeast hypothetical protein YHR106w. </p><p>The 3D structure of <taxon tax_id="562">Escherichia coli</taxon> thioredoxin reductase (TR) has been solved[<cite idref="PUB00004100"/>, <cite idref="PUB00003319"/>].The protein exists as a homodimer, with 3 domains per monomer, whichcorrespond to the FAD-binding, NAD(P)H-binding and central domains ofglutathione reductase (GR) (cf. signature PNDRDTASEI). However, TR lacksthe domain that provides the dimer interface in GR, and forms a completely different dimeric structure. The relative orientation of these domains isvery different in the 2 enzymes: when the FAD-binding domains of TR and GRare superimposed, the NADPH-binding domain of one is rotated by 66 degreeswith respect to the other. The FAD- and NAD(P)H-binding domains have a similar doubly-wound alpha/beta fold, suggesting they evolved by geneduplication [<cite idref="PUB00001601"/>]. While in GR the redox active disulphide is located inthe FAD-binding domain, in TR it lies in the NADPH-binding domain. Thissuggests that the enzymes diverged from an ancestral nucleotide-bindingprotein and acquired their disulphide reductase activities independently [<cite idref="PUB00004100"/>].</p> Pyridine nucleotide-disulphide oxidoreductase, class-II