{PDOC00073}
{PS00076; PYRIDINE_REDOX_1}
{BEGIN}
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* Pyridine nucleotide-disulphide oxidoreductases class-I active site *
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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 to 6]:

 - Glutathione reductase (EC 1.8.1.7) (GR).
 - Higher eukaryotes thioredoxin reductase (EC 1.8.1.9).
 - Trypanothione reductase (EC 1.8.1.12).
 - Lipoamide dehydrogenase (EC 1.8.1.4),  the  E3 component  of alpha-ketoacid
   dehydrogenase complexes.
 - Mercuric reductase (EC 1.16.1.1).

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

-Consensus pattern: G-G-x-C-[LIVA]-x(2)-G-C-[LIVM]-P
                    [The 2 C's form the active site disulfide bond]
-Sequences known to belong to this class detected by the pattern: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.

-Note: 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.

[ 1] Kurlyan J., Krishna T.S.R., Wong L., Guenther B., Pahler A.,
     Williams C.H. Jr., Model P.
     Nature 352:172-174(1991).
[ 2] Rice D.W., Schulz G.E., Guest J.R.
     "Structural relationship between glutathione reductase and lipoamide
     dehydrogenase."
     J. Mol. Biol. 174:483-496(1984).
     PubMed=6546954
[ 3] Brown N.L.
     Trends Biochem. Sci. 10:400-402(1985).
[ 4] Carothers D.J., Pons G., Patel M.S.
     "Dihydrolipoamide dehydrogenase: functional similarities and divergent
     evolution of the pyridine nucleotide-disulfide oxidoreductases."
     Arch. Biochem. Biophys. 268:409-425(1989).
     PubMed=2643922
[ 5] Walsh C.T., Bradley M., Nadeau K.
     "Molecular studies on trypanothione reductase, a target for
     antiparasitic drugs."
     Trends Biochem. Sci. 16:305-309(1991).
     PubMed=1957352
[ 6] Gasdaska P.Y., Gasdaska J.R., Cochran S., Powis G.
     "Cloning and sequencing of a human thioredoxin reductase."
     FEBS Lett. 373:5-9(1995).
     PubMed=7589432
[ 7] Creissen G., Edwards E.A., Enard C., Wellburn A., Mullineaux P.
     "Molecular characterization of glutathione reductase cDNAs from pea
     (Pisum sativum L.)."
     Plant J. 2:129-131(1992).
     PubMed=1303792

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