| Type: | Active_site | Name: | Pyridine nucleotide-disulphide oxidoreductase, class-II, active site |
| Description: | The pyridine nucleotide-disulphide reductases (PNDR) use the isoalloxazine ring of FAD to shuttle reducing equivalents from NAD(P)H to a Cys residuethat 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 [], PNDR can be categorised into 2 groups.Class II includes: prokaryotic and eukaryotic thioredoxin reductases [, ];bacterial alkyl hydroperoxide reductases []; bacterial NADH:dehydrogenases[]; a probable oxidoreductase encoded in the Clostridium pasteurianumrubredoxin operon []; and yeast hypothetical protein YHR106w. The 3D structure of Escherichia colithioredoxin reductase (TR) has been solved [, ].The protein exists as a homodimer, with 3 domains per monomer, which correspond to the FAD-binding, NAD(P)H-binding and central domains ofglutathione 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 GRare 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 []. While in GR the redox active disulphide is located inthe FAD-binding domain, in TR it lies in the NADPH-binding domain. This suggests that the enzymes diverged from an ancestral nucleotide-bindingprotein and acquired their disulphide reductase activities independently [].The sequence around the two cysteines involved in the redox-active disulphide bond is conserved, and is covered by this pattern. | Short Name: | Pyr_nucl-diS_OxRdtase_2_AS |
