1.8.98.1	evolution	a cytoplasmic HdrABC enzyme complex is found in most methanogens, whereas a membrane-bound HdrED complex is found exclusively in members of the order Methanosarcinales. Multiple copies of both Hdr classes are found in all sequenced Methanosarcinales genomes. Evolutionary relationships among the Hdr proteins in methanogens, overview	713055	
1.8.98.1	metabolism	in methanogenic Archaea, the final step of methanogenesis generates methane and a heterodisulfide of coenzyme M and coenzyme B, CoM-S-S-CoB. Reduction of this heterodisulfide by heterodisulfide reductase regenerates HS-CoM and HS-CoB in an exergonic process, methanogenic pathway with hypothesized roles for the heterodisulfide reductase complex, overview. Hdr complexes with F420-nonreducing hydrogenase, formate dehydrogenase, and formyl-methanofuran dehydrogenase, model of complex of proteins that interact with Hdr, overview	-, 713413	
1.8.98.1	metabolism	regardless of the substrate used, all methanogens produce a CoB-S-SCoM heterodisulfide molecule in the last step of methanogenesis. CoBS-S-CoM subsequently must be reduced to regenerate the CoB-SH and CoM-SH thiols that are used as electron donors by methyl-CoM reductase and methyl-CoM methyltransferases. This regeneration reaction is catalysed by the enzyme heterodisulfide reductase	713055	
1.8.98.1	metabolism	the enzyme is involved in ethanol metabolism	-, 742382	
1.8.98.1	additional information	a strain containing His-tagged HdrB1 and a null mutation in hdrB2 grows normally, as does a strain containing His-tagged HdrB2 and a null mutation in hdrB1. Because Hdr is essential, each His-tagged protein must be functional	-, 713413	
1.8.98.1	additional information	either operon HdrED or HdrABC is preferred as the dominant Hdr activity in the cell, or HdrED and HdrABC have specialized physiological functions, dependent on the conditions, overview. Transcription of hdr genes is regulated by methanogenic substrate, overview	713055	
1.8.98.1	physiological function	regardless of the substrate used, all methanogens produce a CoB-S-SCoM heterodisulfide molecule in the last step of methanogenesis. CoBS-S-CoM subsequently must be reduced to regenerate the CoB-SH and CoM-SH thiols that are used as electron donors by methyl-CoM reductase and methyl-CoM methyltransferases. This regeneration reaction is catalysed by the enzyme heterodisulfide reductase. HdrED is essential in Methanosarcina acetivorans, HdrABC is not essential, but contributes to growth and methane production from methylotrophic substrates. The hdrED1 operon is constitutively expressed and required for viability under all growth conditions examined, consistent with HdrED being the primary Hdr. HdrABC is specifically involved in methylotrophic methanogenesis, based on reduced growth and methanogenesis rates of an DELTAhdrA1C1B1 mutant on methylotrophic substrates and downregulation of the genes during growth on acetate, overview	713055	
1.8.98.1	physiological function	the electrons for the enzymatic reaction are delivered to subunit HdrA via formate dehydrogenase Fdh or Hdr-associated hydrogenase Vhu. The delta subunit of hydrogenase, VhuD, is central to the interaction of both enzymes with HdrA. In the absence of Vhu, growth on hydrogen still occurs but involves F420-reducing hydrogenase	725292