title: The heterodisulfide reductase from Methanobacterium thermoautotrophicum contains sequence motifs characteristic of pyridine-nucleotide-dependent thioredoxin reductases.
abstract: The genes hdrA, hdrB and hdrC, encoding the three subunits of the iron-sulfur flavoprotein heterodisulfide reductase, have been cloned and sequenced. HdrA (72.19 kDa) was found to contain a region of amino acid sequence highly similar to the FAD-binding domain of pyridine-nucleotide-dependent disulfide oxidoreductases. Additionally, 110 amino acids C-terminal to the FAD-binding consensus, a short polypeptide stretch (VX2CATID) was detected which shows similarity to the region of thioredoxine reductase that contains the active-site cysteine residues (VX2CATCD). These findings suggest that HdrA harbors the site of heterodisulfide reduction and that the catalytic mechanism of the enzyme is similar to that of pyridine-nucleotide-dependent thioredoxin reductase. HdrA was additionally found to contain four copies of the sequence motif CX2CX2CX3C(P), indicating the presence of four [4Fe-4S] clusters. Two such sequence motifs were also present in HdrC (21.76 kDa), the N-terminal amino acid sequence of which showed sequence similarity to the gamma-subunit of the anaerobic glycerol-3-phosphate dehydrogenase of Escherichia coli. HdrC is therefore considered to be an electron carrier protein that contains two [4Fe-4S] clusters. HdrB (33.46 kDa) did not show sequence similarity to other known proteins, but appears to possess a C-terminal hydrophobic alpha-helix that might function as a membrane anchor. Although hdrB and hdrC are juxtaposed, these genes are not near hdrA.
authors.affiliation: Max-Planck-Institut für terrestrische Mikrobiologie und Laboratorium für Mikrobiologie des Fachbereichs Biologie, Philipps-Universität Marburg, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Hedderich
authors.forename: J
authors.initials: J
authors.lastname: Koch
authors.forename: D
authors.initials: D
authors.lastname: Linder
authors.forename: R K
authors.initials: RK
authors.lastname: Thauer
mesh_terms: D000595:Amino Acid Sequence; D000693:Anaerobiosis; D001419:Bacteria / Q000201:enzymology / Q000235:genetics; D001483:Base Sequence; D001665:Binding Sites; D003545:Cysteine; D004926:Escherichia coli / Q000201:enzymology / Q000235:genetics; D005798:Genes, Bacterial; D016680:Genome, Bacterial; D005993:Glycerolphosphate Dehydrogenase / Q000737:chemistry / Q000235:genetics; D007506:Iron-Sulfur Proteins / Q000096:biosynthesis / Q000737:chemistry* / Q000235:genetics; D046911:Macromolecular Substances; D017014:Methanobacterium / Q000201:enzymology* / Q000235:genetics; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes; D010088:Oxidoreductases / Q000096:biosynthesis / Q000737:chemistry* / Q000235:genetics; D015183:Restriction Mapping; D017386:Sequence Homology, Amino Acid; D013880:Thioredoxin-Disulfide Reductase / Q000096:biosynthesis / Q000737:chemistry*
chemical_list: D007506:Iron-Sulfur Proteins; D046911:Macromolecular Substances; D015345:Oligonucleotide Probes; D010088:Oxidoreductases; D005993:Glycerolphosphate Dehydrogenase; C087171:heterodisulfide reductase; D013880:Thioredoxin-Disulfide Reductase; D003545:Cysteine