PROSITE documentation PDOC00073
Pyridine nucleotide-disulphide oxidoreductases class-I active site


The pyridine nucleotide-disulphide oxidoreductases are FAD flavoproteins which contains a pair of redox-active cysteines involved in the transfer of reducing equivalents from the FAD cofactor to the substrate. On the basis of sequence and structural similarities [1] these enzymes can be classified into two categories. The first category groups together the following enzymes [2,3,4,5,6]:

  • Glutathione reductase (EC (GR).
  • Higher eukaryotes thioredoxin reductase (EC
  • Trypanothione reductase (EC
  • Lipoamide dehydrogenase (EC, the E3 component of α-ketoacid dehydrogenase complexes.
  • Mercuric reductase (EC

The sequence around the two cysteines involved in the redox-active disulfide bond is conserved and can be used as a signature pattern.


In positions 6 and 7 of the pattern all known sequences have Asn-(Val/ Ile) with the exception of GR from plant chloroplasts and from cyanobacteria which have Ile-Arg [7].

Last update:

May 2004 / Text revised.


Technical section

PROSITE method (with tools and information) covered by this documentation:

PYRIDINE_REDOX_1, PS00076; Pyridine nucleotide-disulphide oxidoreductases class-I active site  (PATTERN)


1AuthorsKurlyan J. Krishna T.S.R. Wong L. Guenther B. Pahler A. Williams C.H. Jr. Model P.
SourceNature 352:172-174(1991).

2AuthorsRice D.W. Schulz G.E. Guest J.R.
TitleStructural relationship between glutathione reductase and lipoamide dehydrogenase.
SourceJ. Mol. Biol. 174:483-496(1984).
PubMed ID6546954

3AuthorsBrown N.L.
SourceTrends Biochem. Sci. 10:400-402(1985).

4AuthorsCarothers D.J. Pons G. Patel M.S.
TitleDihydrolipoamide dehydrogenase: functional similarities and divergent evolution of the pyridine nucleotide-disulfide oxidoreductases.
SourceArch. Biochem. Biophys. 268:409-425(1989).
PubMed ID2643922

5AuthorsWalsh C.T. Bradley M. Nadeau K.
TitleMolecular studies on trypanothione reductase, a target for antiparasitic drugs.
SourceTrends Biochem. Sci. 16:305-309(1991).
PubMed ID1957352

6AuthorsGasdaska P.Y. Gasdaska J.R. Cochran S. Powis G.
TitleCloning and sequencing of a human thioredoxin reductase.
SourceFEBS Lett. 373:5-9(1995).
PubMed ID7589432

7AuthorsCreissen G. Edwards E.A. Enard C. Wellburn A. Mullineaux P.
TitleMolecular characterization of glutathione reductase cDNAs from pea (Pisum sativum L.).
SourcePlant J. 2:129-131(1992).
PubMed ID1303792

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