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2 reduced ferredoxin [iron-sulfur] cluster + CoB + CoM + 2 H+
2 H2 + 2 oxidized ferredoxin [iron-sulfur] cluster + CoM-S-S-CoB
2 reduced ferredoxin [iron-sulfur] cluster + CoM-S-S-CoB + 2 H+
2 oxidized ferredoxin [iron-sulfur] cluster + CoB + CoM
oxidized ferredoxin [iron-sulfur] cluster + CoB + CoM
reduced ferredoxin [iron-sulfur] cluster + CoM-S-S-CoB + H+
oxidized methyl viologen + CoB + CoM
reduced methyl viologen + CoM-S-S-CoB + H+
reduced ferredoxin [iron-sulfur] cluster + CoM-S-S-CoB + H+
oxidized ferredoxin [iron-sulfur] cluster + CoB + CoM
reduced ferredoxin [iron-sulfur] cluster + DsrC-S-S-DsrC + H+
oxidized ferredoxin [iron-sulfur] cluster + DsrC + DsrC
additional information
?
-
2 reduced ferredoxin [iron-sulfur] cluster + CoB + CoM + 2 H+
2 H2 + 2 oxidized ferredoxin [iron-sulfur] cluster + CoM-S-S-CoB
-
-
-
?
2 reduced ferredoxin [iron-sulfur] cluster + CoB + CoM + 2 H+
2 H2 + 2 oxidized ferredoxin [iron-sulfur] cluster + CoM-S-S-CoB
-
-
-
?
2 reduced ferredoxin [iron-sulfur] cluster + CoM-S-S-CoB + 2 H+
2 oxidized ferredoxin [iron-sulfur] cluster + CoB + CoM
P60200; Q58153; Q58273; Q58154; Q58274
-
-
-
?
2 reduced ferredoxin [iron-sulfur] cluster + CoM-S-S-CoB + 2 H+
2 oxidized ferredoxin [iron-sulfur] cluster + CoB + CoM
P60200; Q58153; Q58273; Q58154; Q58274
-
-
-
?
2 reduced ferredoxin [iron-sulfur] cluster + CoM-S-S-CoB + 2 H+
2 oxidized ferredoxin [iron-sulfur] cluster + CoB + CoM
P60200; Q58153; Q58273; Q58154; Q58274
-
-
-
?
2 reduced ferredoxin [iron-sulfur] cluster + CoM-S-S-CoB + 2 H+
2 oxidized ferredoxin [iron-sulfur] cluster + CoB + CoM
P60200; Q58153; Q58273; Q58154; Q58274
-
-
-
?
2 reduced ferredoxin [iron-sulfur] cluster + CoM-S-S-CoB + 2 H+
2 oxidized ferredoxin [iron-sulfur] cluster + CoB + CoM
P60200; Q58153; Q58273; Q58154; Q58274
-
-
-
?
2 reduced ferredoxin [iron-sulfur] cluster + CoM-S-S-CoB + 2 H+
2 oxidized ferredoxin [iron-sulfur] cluster + CoB + CoM
P60200; Q58153; Q58273; Q58154; Q58274
-
-
-
?
2 reduced ferredoxin [iron-sulfur] cluster + CoM-S-S-CoB + 2 H+
2 oxidized ferredoxin [iron-sulfur] cluster + CoB + CoM
-
-
-
-
?
2 reduced ferredoxin [iron-sulfur] cluster + CoM-S-S-CoB + 2 H+
2 oxidized ferredoxin [iron-sulfur] cluster + CoB + CoM
-
-
-
?
2 reduced ferredoxin [iron-sulfur] cluster + CoM-S-S-CoB + 2 H+
2 oxidized ferredoxin [iron-sulfur] cluster + CoB + CoM
-
-
-
-
?
2 reduced ferredoxin [iron-sulfur] cluster + CoM-S-S-CoB + 2 H+
2 oxidized ferredoxin [iron-sulfur] cluster + CoB + CoM
-
-
-
?
2 reduced ferredoxin [iron-sulfur] cluster + CoM-S-S-CoB + 2 H+
2 oxidized ferredoxin [iron-sulfur] cluster + CoB + CoM
-
-
-
?
2 reduced ferredoxin [iron-sulfur] cluster + CoM-S-S-CoB + 2 H+
2 oxidized ferredoxin [iron-sulfur] cluster + CoB + CoM
-
-
-
?
2 reduced ferredoxin [iron-sulfur] cluster + CoM-S-S-CoB + 2 H+
2 oxidized ferredoxin [iron-sulfur] cluster + CoB + CoM
-
-
-
?
oxidized ferredoxin [iron-sulfur] cluster + CoB + CoM
reduced ferredoxin [iron-sulfur] cluster + CoM-S-S-CoB + H+
-
-
-
-
?
oxidized ferredoxin [iron-sulfur] cluster + CoB + CoM
reduced ferredoxin [iron-sulfur] cluster + CoM-S-S-CoB + H+
-
-
-
-
?
oxidized ferredoxin [iron-sulfur] cluster + CoB + CoM
reduced ferredoxin [iron-sulfur] cluster + CoM-S-S-CoB + H+
-
-
-
-
?
oxidized ferredoxin [iron-sulfur] cluster + CoB + CoM
reduced ferredoxin [iron-sulfur] cluster + CoM-S-S-CoB + H+
-
-
-
-
?
oxidized ferredoxin [iron-sulfur] cluster + CoB + CoM
reduced ferredoxin [iron-sulfur] cluster + CoM-S-S-CoB + H+
-
-
-
-
r
oxidized ferredoxin [iron-sulfur] cluster + CoB + CoM
reduced ferredoxin [iron-sulfur] cluster + CoM-S-S-CoB + H+
-
-
-
-
?
oxidized ferredoxin [iron-sulfur] cluster + CoB + CoM
reduced ferredoxin [iron-sulfur] cluster + CoM-S-S-CoB + H+
-
-
-
?
oxidized methyl viologen + CoB + CoM
reduced methyl viologen + CoM-S-S-CoB + H+
-
-
-
-
?
oxidized methyl viologen + CoB + CoM
reduced methyl viologen + CoM-S-S-CoB + H+
-
-
-
-
?
reduced ferredoxin [iron-sulfur] cluster + CoM-S-S-CoB + H+
oxidized ferredoxin [iron-sulfur] cluster + CoB + CoM
-
-
-
-
?
reduced ferredoxin [iron-sulfur] cluster + CoM-S-S-CoB + H+
oxidized ferredoxin [iron-sulfur] cluster + CoB + CoM
-
-
-
-
?
reduced ferredoxin [iron-sulfur] cluster + CoM-S-S-CoB + H+
oxidized ferredoxin [iron-sulfur] cluster + CoB + CoM
-
-
-
-
r
reduced ferredoxin [iron-sulfur] cluster + DsrC-S-S-DsrC + H+
oxidized ferredoxin [iron-sulfur] cluster + DsrC + DsrC
-
-
-
-
?
reduced ferredoxin [iron-sulfur] cluster + DsrC-S-S-DsrC + H+
oxidized ferredoxin [iron-sulfur] cluster + DsrC + DsrC
-
-
-
-
?
additional information
?
-
-
thiols are only produced when membranes of Methanomassiliicoccus luminyensis, HdrD, Fd, and IOR are present. In the absence of Fd, HdrD, or washed membranes, thiol formation is very low indicating that all above-mentioned components are necessary for an effective electron transfer from Fdred to CoM-S-S-CoB. Fd:heterodisulfide reductase activity is measured by the oxidation of Fdred as the initial reaction and thiol formation by CoM-S-S-CoB reduction as a final reaction of the proposed electron transport chain. At least one membrane-bound enzyme is needed for electron transport
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-
-
additional information
?
-
Hdr receives two electrons from the oxidation of H2 through MvhAGD [NiFe]-hydrogenase, cf. EC 1.8.98.4
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-
-
additional information
?
-
heterodisulfide reductase (HdrABC) reduces the disulfide bond with electrons supplied from the oxidation of 2H2 or 2HCO2H catalyzed by F420-independent hydrogenase or Fdh. The exergonic reduction of CoMS-SCoB drives the endergonic reduction of CO2 in the first step via FBEB by HdrABC
-
-
-
additional information
?
-
Hdr receives two electrons from the oxidation of H2 through MvhAGD [NiFe]-hydrogenase, cf. EC 1.8.98.4
-
-
-
additional information
?
-
heterodisulfide reductase (HdrABC) reduces the disulfide bond with electrons supplied from the oxidation of 2H2 or 2HCO2H catalyzed by F420-independent hydrogenase or Fdh. The exergonic reduction of CoMS-SCoB drives the endergonic reduction of CO2 in the first step via FBEB by HdrABC
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-
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
2 reduced ferredoxin [iron-sulfur] cluster + CoB + CoM + 2 H+
2 H2 + 2 oxidized ferredoxin [iron-sulfur] cluster + CoM-S-S-CoB
2 reduced ferredoxin [iron-sulfur] cluster + CoM-S-S-CoB + 2 H+
2 oxidized ferredoxin [iron-sulfur] cluster + CoB + CoM
oxidized ferredoxin [iron-sulfur] cluster + CoB + CoM
reduced ferredoxin [iron-sulfur] cluster + CoM-S-S-CoB + H+
reduced ferredoxin [iron-sulfur] cluster + CoM-S-S-CoB + H+
oxidized ferredoxin [iron-sulfur] cluster + CoB + CoM
reduced ferredoxin [iron-sulfur] cluster + DsrC-S-S-DsrC + H+
oxidized ferredoxin [iron-sulfur] cluster + DsrC + DsrC
additional information
?
-
2 reduced ferredoxin [iron-sulfur] cluster + CoB + CoM + 2 H+
2 H2 + 2 oxidized ferredoxin [iron-sulfur] cluster + CoM-S-S-CoB
-
-
-
?
2 reduced ferredoxin [iron-sulfur] cluster + CoB + CoM + 2 H+
2 H2 + 2 oxidized ferredoxin [iron-sulfur] cluster + CoM-S-S-CoB
-
-
-
?
2 reduced ferredoxin [iron-sulfur] cluster + CoM-S-S-CoB + 2 H+
2 oxidized ferredoxin [iron-sulfur] cluster + CoB + CoM
P60200; Q58153; Q58273; Q58154; Q58274
-
-
-
?
2 reduced ferredoxin [iron-sulfur] cluster + CoM-S-S-CoB + 2 H+
2 oxidized ferredoxin [iron-sulfur] cluster + CoB + CoM
P60200; Q58153; Q58273; Q58154; Q58274
-
-
-
?
2 reduced ferredoxin [iron-sulfur] cluster + CoM-S-S-CoB + 2 H+
2 oxidized ferredoxin [iron-sulfur] cluster + CoB + CoM
P60200; Q58153; Q58273; Q58154; Q58274
-
-
-
?
2 reduced ferredoxin [iron-sulfur] cluster + CoM-S-S-CoB + 2 H+
2 oxidized ferredoxin [iron-sulfur] cluster + CoB + CoM
P60200; Q58153; Q58273; Q58154; Q58274
-
-
-
?
2 reduced ferredoxin [iron-sulfur] cluster + CoM-S-S-CoB + 2 H+
2 oxidized ferredoxin [iron-sulfur] cluster + CoB + CoM
P60200; Q58153; Q58273; Q58154; Q58274
-
-
-
?
2 reduced ferredoxin [iron-sulfur] cluster + CoM-S-S-CoB + 2 H+
2 oxidized ferredoxin [iron-sulfur] cluster + CoB + CoM
P60200; Q58153; Q58273; Q58154; Q58274
-
-
-
?
2 reduced ferredoxin [iron-sulfur] cluster + CoM-S-S-CoB + 2 H+
2 oxidized ferredoxin [iron-sulfur] cluster + CoB + CoM
-
-
-
-
?
2 reduced ferredoxin [iron-sulfur] cluster + CoM-S-S-CoB + 2 H+
2 oxidized ferredoxin [iron-sulfur] cluster + CoB + CoM
-
-
-
?
2 reduced ferredoxin [iron-sulfur] cluster + CoM-S-S-CoB + 2 H+
2 oxidized ferredoxin [iron-sulfur] cluster + CoB + CoM
-
-
-
-
?
2 reduced ferredoxin [iron-sulfur] cluster + CoM-S-S-CoB + 2 H+
2 oxidized ferredoxin [iron-sulfur] cluster + CoB + CoM
-
-
-
?
2 reduced ferredoxin [iron-sulfur] cluster + CoM-S-S-CoB + 2 H+
2 oxidized ferredoxin [iron-sulfur] cluster + CoB + CoM
-
-
-
?
2 reduced ferredoxin [iron-sulfur] cluster + CoM-S-S-CoB + 2 H+
2 oxidized ferredoxin [iron-sulfur] cluster + CoB + CoM
-
-
-
?
2 reduced ferredoxin [iron-sulfur] cluster + CoM-S-S-CoB + 2 H+
2 oxidized ferredoxin [iron-sulfur] cluster + CoB + CoM
-
-
-
?
oxidized ferredoxin [iron-sulfur] cluster + CoB + CoM
reduced ferredoxin [iron-sulfur] cluster + CoM-S-S-CoB + H+
-
-
-
-
?
oxidized ferredoxin [iron-sulfur] cluster + CoB + CoM
reduced ferredoxin [iron-sulfur] cluster + CoM-S-S-CoB + H+
-
-
-
-
?
oxidized ferredoxin [iron-sulfur] cluster + CoB + CoM
reduced ferredoxin [iron-sulfur] cluster + CoM-S-S-CoB + H+
-
-
-
-
?
oxidized ferredoxin [iron-sulfur] cluster + CoB + CoM
reduced ferredoxin [iron-sulfur] cluster + CoM-S-S-CoB + H+
-
-
-
-
?
oxidized ferredoxin [iron-sulfur] cluster + CoB + CoM
reduced ferredoxin [iron-sulfur] cluster + CoM-S-S-CoB + H+
-
-
-
-
r
oxidized ferredoxin [iron-sulfur] cluster + CoB + CoM
reduced ferredoxin [iron-sulfur] cluster + CoM-S-S-CoB + H+
-
-
-
-
?
oxidized ferredoxin [iron-sulfur] cluster + CoB + CoM
reduced ferredoxin [iron-sulfur] cluster + CoM-S-S-CoB + H+
-
-
-
?
reduced ferredoxin [iron-sulfur] cluster + CoM-S-S-CoB + H+
oxidized ferredoxin [iron-sulfur] cluster + CoB + CoM
-
-
-
-
?
reduced ferredoxin [iron-sulfur] cluster + CoM-S-S-CoB + H+
oxidized ferredoxin [iron-sulfur] cluster + CoB + CoM
-
-
-
-
?
reduced ferredoxin [iron-sulfur] cluster + CoM-S-S-CoB + H+
oxidized ferredoxin [iron-sulfur] cluster + CoB + CoM
-
-
-
-
r
reduced ferredoxin [iron-sulfur] cluster + DsrC-S-S-DsrC + H+
oxidized ferredoxin [iron-sulfur] cluster + DsrC + DsrC
-
-
-
-
?
reduced ferredoxin [iron-sulfur] cluster + DsrC-S-S-DsrC + H+
oxidized ferredoxin [iron-sulfur] cluster + DsrC + DsrC
-
-
-
-
?
additional information
?
-
Hdr receives two electrons from the oxidation of H2 through MvhAGD [NiFe]-hydrogenase, cf. EC 1.8.98.4
-
-
-
additional information
?
-
Hdr receives two electrons from the oxidation of H2 through MvhAGD [NiFe]-hydrogenase, cf. EC 1.8.98.4
-
-
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
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evolution
conservation of Hdr and Fmd structures suggests that the complex of both is common among hydrogenotrophic methanogens
evolution
-
HdrA homologues are found in many other microorganisms, i.e. anaerobic methanotrophic archaea, sulfate-reducing bacteria and archaea, sulfur-oxidizing bacteria, acetogenic bacteria, knallgas bacteria, and metal-reducing bacteria
evolution
HdrA homologues are found in many other microorganisms, i.e. anaerobic methanotrophic archaea, sulfate-reducing bacteria and archaea, sulfur-oxidizing bacteria, acetogenic bacteria, knallgas bacteria, and metal-reducing bacteria. The fifth cysteine Cys197' of Methanothermococcus thermolithotrophicus HdrA is exchanged for a selenocysteine in HdrA from Methanocaldococcus jannaschii
evolution
P60200; Q58153; Q58273; Q58154; Q58274
HdrA homologues are found in many other microorganisms, i.e. anaerobic methanotrophic archaea, sulfate-reducing bacteria and archaea, sulfur-oxidizing bacteria, acetogenic bacteria, knallgas bacteria, and metal-reducing bacteria. The fifth cysteine Cys197' of Methanothermococcus thermolithotrophicus HdrA is exchanged for a selenocysteine in HdrA from Methanocaldococcus jannaschii
evolution
-
the energy-conserving system in Methanomassiliicoccus luminyensis is unique, and the enzymes involved in this process are not found in this combination in members of the other methanogenic orders. The composition of the enzymes involved in ion translocation across the cytoplasmic membrane is different from all other methanogenic archaea
evolution
-
HdrA homologues are found in many other microorganisms, i.e. anaerobic methanotrophic archaea, sulfate-reducing bacteria and archaea, sulfur-oxidizing bacteria, acetogenic bacteria, knallgas bacteria, and metal-reducing bacteria. The fifth cysteine Cys197' of Methanothermococcus thermolithotrophicus HdrA is exchanged for a selenocysteine in HdrA from Methanocaldococcus jannaschii
-
evolution
-
HdrA homologues are found in many other microorganisms, i.e. anaerobic methanotrophic archaea, sulfate-reducing bacteria and archaea, sulfur-oxidizing bacteria, acetogenic bacteria, knallgas bacteria, and metal-reducing bacteria. The fifth cysteine Cys197' of Methanothermococcus thermolithotrophicus HdrA is exchanged for a selenocysteine in HdrA from Methanocaldococcus jannaschii
-
evolution
-
HdrA homologues are found in many other microorganisms, i.e. anaerobic methanotrophic archaea, sulfate-reducing bacteria and archaea, sulfur-oxidizing bacteria, acetogenic bacteria, knallgas bacteria, and metal-reducing bacteria. The fifth cysteine Cys197' of Methanothermococcus thermolithotrophicus HdrA is exchanged for a selenocysteine in HdrA from Methanocaldococcus jannaschii
-
evolution
-
HdrA homologues are found in many other microorganisms, i.e. anaerobic methanotrophic archaea, sulfate-reducing bacteria and archaea, sulfur-oxidizing bacteria, acetogenic bacteria, knallgas bacteria, and metal-reducing bacteria. The fifth cysteine Cys197' of Methanothermococcus thermolithotrophicus HdrA is exchanged for a selenocysteine in HdrA from Methanocaldococcus jannaschii
-
evolution
-
HdrA homologues are found in many other microorganisms, i.e. anaerobic methanotrophic archaea, sulfate-reducing bacteria and archaea, sulfur-oxidizing bacteria, acetogenic bacteria, knallgas bacteria, and metal-reducing bacteria. The fifth cysteine Cys197' of Methanothermococcus thermolithotrophicus HdrA is exchanged for a selenocysteine in HdrA from Methanocaldococcus jannaschii
-
evolution
-
HdrA homologues are found in many other microorganisms, i.e. anaerobic methanotrophic archaea, sulfate-reducing bacteria and archaea, sulfur-oxidizing bacteria, acetogenic bacteria, knallgas bacteria, and metal-reducing bacteria. The fifth cysteine Cys197' of Methanothermococcus thermolithotrophicus HdrA is exchanged for a selenocysteine in HdrA from Methanocaldococcus jannaschii
-
metabolism
a methyl-CoM reductase catalyzes the reductive resolution of methyl-CoM to form methane and a disulfide CoM conjugate of coenzyme B (CoM-S-S-CoB). This is the penultimate conserved step in all pathways of methanogenesis leaving only the reduction of CoM-S-S-CoB and recycling of the key methanogen cofactors CoM and CoB.. The reduction of CoM-S-S-CoB is often coupled to the oxidation of H2, an exergonic reaction with a significant negative free-energy change. Methanogens conserve the free energy by coupling this exergonic reaction to the hydrogen-dependent reduction of ferredoxin, which on its own would be an endergonic reaction. These reactions are coupled through flavin-based electron bifurcation that maximizes the energy efficiency in hydrogenotrophic methanogenesis. Heterodisulfide reductase (Hdr) is the valve that closes the cycle of methanogenesis, allowing energy to be conserved and providing an energetic advantage to the cell. Hdr catalyzes flavin-based electron bifurcation that results in the exergonic reduction of heterodisulfide (CoMS-S-CoB) coupled to the endergonic reduction of ferredoxin. In the proposed mechanism of bifurcation, the bifurcation-site flavin receives two electrons from a single donor, and then bifurcate one electron to reduce the heterodisulfide and one electron to reduce ferredoxin. Another round of bifurcation results in the complete reduction of CoM-S-S-CoB to HS-CoB and HS-CoM and 2 equivalents of reduced ferredoxin. Hdr receives two electrons from the oxidation of H2 through MvhAGD [NiFe]-hydrogenase EC 1.8.98.4
metabolism
-
in methanogenic archaea, the carbon dioxide (CO2) fixation and methane-forming steps are linked through the heterodisulfide reductase (HdrABC)-[NiFe]-hydrogenase (MvhAGD) complex that uses flavin-based electron bifurcation to reduce ferredoxin and the heterodisulfide of coenzymes M and B
metabolism
in methanogenic archaea, the carbon dioxide (CO2) fixation and methane-forming steps are linked through the heterodisulfide reductase (HdrABC)-[NiFe]-hydrogenase (MvhAGD) complex that uses flavin-based electron bifurcation to reduce ferredoxin and the heterodisulfide of coenzymes M and B
metabolism
P60200; Q58153; Q58273; Q58154; Q58274
in methanogenic archaea, the carbon dioxide (CO2) fixation and methane-forming steps are linked through the heterodisulfide reductase (HdrABC)-[NiFe]-hydrogenase (MvhAGD) complex that uses flavin-based electron bifurcation to reduce ferredoxin and the heterodisulfide of coenzymes M and B
metabolism
reduction of the disulfide of coenzyme M and coenzyme B (CoMS-SCoB) by heterodisulfide reductases (HdrED and HdrABC) is the final step in all methanogenic pathways. Flavin-based electron bifurcation (FBEB) by soluble HdrABC homologues play additional roles in driving essential endergonic reactions at the expense of the exergonic reduction of CoMS-SCoM. In the first step of the CO2 reduction pathway, HdrABC complexed with hydrogenase (EC 1.12.1.2) or formate dehydrogenase generates reduces ferredoxin (Fdx2-) for the endergonic reduction of CO2 coupled to the exergonic reduction of CoMS-SCoB dependent on FBEB of electrons from H2 or formate, respectively. Roles for HdrABC:hydrogenase complexes are also proposed for pathways wherein the methyl group of methanol is reduced to methane with electrons from H2. The HdrABC complexes catalyze FBEB-dependent oxidation of H2 for the endergonic reduction of Fdx driven by the exergonic reduction of CoMS-SCoB. The Fdx2- supplies electrons for reduction of the methyl group to methane. In H2- independent pathways, threefourths of the methyl groups are oxidized producing Fdx2- and reduced coenzyme F420 (F420H2). The F420H2 donates electrons for reduction of the remaining methyl groups to methane requiring transfer of electrons from Fdx2- to F420. HdrA1B1C1 is proposed to catalyze FBEB-dependent oxidation of Fdx2- for the endergonic reduction of F420 driven by the exergonic reduction of CoMS-SCoB, see for EC 1.8.98.4. In H2- independent acetotrophic pathways (EC 1.8.98.5), the methyl group of acetate is reduced to methane with electrons derived from oxidation of the carbonyl group mediated by Fdx. Electron transport involves a membrane-bound complex (Rnf) that oxidizes Fdx2- and generates a NaC gradient driving ATP synthesis. It is postulated that F420 is reduced by Rnf requiring HdrA2B2C2 catalyzing FBEB-dependent oxidation of F420H2 for the endergonic reduction of Fdx driven by the exergonic reduction of CoMS-SCoB (EC 1.8.98.4). The Fdx2- is recycled by Rnf and HdrA2B2C2 thereby conserving energy. The HdrA2B2C2 is also proposed to play a role in Fe(III)-dependent reverse methanogenesis. A flavin-based electron confurcating (FBEC) HdrABC complex is proposed for nitrate-dependent reverse methanogenesis in which the oxidation of CoM-SH/CoB-SH and Fdx2- is coupled to reduction of F420. The F420H2 donates electrons to a membrane complex that generates a proton gradient driving ATP synthesis
metabolism
the first reaction of the methanogenic pathway from carbon dioxide (CO2) is the reduction and condensation of CO2 to formyl-methanofuran, catalyzed by formyl-methanofuran dehydrogenase (Fmd, EC 1.12.7.2). Strongly reducing electrons for this reaction are generated by heterodisulfide reductase (Hdr, EC 1.8.7.3) in complex with hydrogenase or formate dehydrogenase (Fdh) using a flavin-based electron-bifurcation mechanism
metabolism
-
the process of methanogenesis in Methanomassiliicoccus luminyensis involves the transfer of methyl group from methanol or methylamines to 2-mercaptoethanesulfonate (HSCoM). The resulting methyl-S-CoM is reduced to methane by the methyl-CoM reductase which uses 7-mercaptoheptanoylthreonine phosphate (HS-CoB) as a reductant and forms the heterodisulfide (CoM-S-SCoB). The membrane-bound electron transport is based on the headless Fpo complex, which accepts electrons from Fdred and channels these electrons to the heterodisulfide reductase HdrD. And HdrD reduces the final electron acceptor the heterodisulfide (CoB-S-S-CoM)
metabolism
-
in methanogenic archaea, the carbon dioxide (CO2) fixation and methane-forming steps are linked through the heterodisulfide reductase (HdrABC)-[NiFe]-hydrogenase (MvhAGD) complex that uses flavin-based electron bifurcation to reduce ferredoxin and the heterodisulfide of coenzymes M and B
-
metabolism
-
in methanogenic archaea, the carbon dioxide (CO2) fixation and methane-forming steps are linked through the heterodisulfide reductase (HdrABC)-[NiFe]-hydrogenase (MvhAGD) complex that uses flavin-based electron bifurcation to reduce ferredoxin and the heterodisulfide of coenzymes M and B
-
metabolism
-
in methanogenic archaea, the carbon dioxide (CO2) fixation and methane-forming steps are linked through the heterodisulfide reductase (HdrABC)-[NiFe]-hydrogenase (MvhAGD) complex that uses flavin-based electron bifurcation to reduce ferredoxin and the heterodisulfide of coenzymes M and B
-
metabolism
-
in methanogenic archaea, the carbon dioxide (CO2) fixation and methane-forming steps are linked through the heterodisulfide reductase (HdrABC)-[NiFe]-hydrogenase (MvhAGD) complex that uses flavin-based electron bifurcation to reduce ferredoxin and the heterodisulfide of coenzymes M and B
-
metabolism
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a methyl-CoM reductase catalyzes the reductive resolution of methyl-CoM to form methane and a disulfide CoM conjugate of coenzyme B (CoM-S-S-CoB). This is the penultimate conserved step in all pathways of methanogenesis leaving only the reduction of CoM-S-S-CoB and recycling of the key methanogen cofactors CoM and CoB.. The reduction of CoM-S-S-CoB is often coupled to the oxidation of H2, an exergonic reaction with a significant negative free-energy change. Methanogens conserve the free energy by coupling this exergonic reaction to the hydrogen-dependent reduction of ferredoxin, which on its own would be an endergonic reaction. These reactions are coupled through flavin-based electron bifurcation that maximizes the energy efficiency in hydrogenotrophic methanogenesis. Heterodisulfide reductase (Hdr) is the valve that closes the cycle of methanogenesis, allowing energy to be conserved and providing an energetic advantage to the cell. Hdr catalyzes flavin-based electron bifurcation that results in the exergonic reduction of heterodisulfide (CoMS-S-CoB) coupled to the endergonic reduction of ferredoxin. In the proposed mechanism of bifurcation, the bifurcation-site flavin receives two electrons from a single donor, and then bifurcate one electron to reduce the heterodisulfide and one electron to reduce ferredoxin. Another round of bifurcation results in the complete reduction of CoM-S-S-CoB to HS-CoB and HS-CoM and 2 equivalents of reduced ferredoxin. Hdr receives two electrons from the oxidation of H2 through MvhAGD [NiFe]-hydrogenase EC 1.8.98.4
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metabolism
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reduction of the disulfide of coenzyme M and coenzyme B (CoMS-SCoB) by heterodisulfide reductases (HdrED and HdrABC) is the final step in all methanogenic pathways. Flavin-based electron bifurcation (FBEB) by soluble HdrABC homologues play additional roles in driving essential endergonic reactions at the expense of the exergonic reduction of CoMS-SCoM. In the first step of the CO2 reduction pathway, HdrABC complexed with hydrogenase (EC 1.12.1.2) or formate dehydrogenase generates reduces ferredoxin (Fdx2-) for the endergonic reduction of CO2 coupled to the exergonic reduction of CoMS-SCoB dependent on FBEB of electrons from H2 or formate, respectively. Roles for HdrABC:hydrogenase complexes are also proposed for pathways wherein the methyl group of methanol is reduced to methane with electrons from H2. The HdrABC complexes catalyze FBEB-dependent oxidation of H2 for the endergonic reduction of Fdx driven by the exergonic reduction of CoMS-SCoB. The Fdx2- supplies electrons for reduction of the methyl group to methane. In H2- independent pathways, threefourths of the methyl groups are oxidized producing Fdx2- and reduced coenzyme F420 (F420H2). The F420H2 donates electrons for reduction of the remaining methyl groups to methane requiring transfer of electrons from Fdx2- to F420. HdrA1B1C1 is proposed to catalyze FBEB-dependent oxidation of Fdx2- for the endergonic reduction of F420 driven by the exergonic reduction of CoMS-SCoB, see for EC 1.8.98.4. In H2- independent acetotrophic pathways (EC 1.8.98.5), the methyl group of acetate is reduced to methane with electrons derived from oxidation of the carbonyl group mediated by Fdx. Electron transport involves a membrane-bound complex (Rnf) that oxidizes Fdx2- and generates a NaC gradient driving ATP synthesis. It is postulated that F420 is reduced by Rnf requiring HdrA2B2C2 catalyzing FBEB-dependent oxidation of F420H2 for the endergonic reduction of Fdx driven by the exergonic reduction of CoMS-SCoB (EC 1.8.98.4). The Fdx2- is recycled by Rnf and HdrA2B2C2 thereby conserving energy. The HdrA2B2C2 is also proposed to play a role in Fe(III)-dependent reverse methanogenesis. A flavin-based electron confurcating (FBEC) HdrABC complex is proposed for nitrate-dependent reverse methanogenesis in which the oxidation of CoM-SH/CoB-SH and Fdx2- is coupled to reduction of F420. The F420H2 donates electrons to a membrane complex that generates a proton gradient driving ATP synthesis
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metabolism
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in methanogenic archaea, the carbon dioxide (CO2) fixation and methane-forming steps are linked through the heterodisulfide reductase (HdrABC)-[NiFe]-hydrogenase (MvhAGD) complex that uses flavin-based electron bifurcation to reduce ferredoxin and the heterodisulfide of coenzymes M and B
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metabolism
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in methanogenic archaea, the carbon dioxide (CO2) fixation and methane-forming steps are linked through the heterodisulfide reductase (HdrABC)-[NiFe]-hydrogenase (MvhAGD) complex that uses flavin-based electron bifurcation to reduce ferredoxin and the heterodisulfide of coenzymes M and B
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physiological function
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energy conservation in the gut microbe Methanomassiliicoccus luminyensis is based on membrane-bound ferredoxin oxidation coupled to heterodisulfide reduction. Energy transduction is dependent on a membrane-bound ferredoxin:heterodisulfide oxidoreductase composed of reduced ferredoxin as an electron donor, at least one protein in the membrane fraction and the heterodisulfide reductase HdrD, which reduces the electron acceptor CoMS-S-CoB. Electron transfer of this respiratory chain proceeds with a rate of 145 nmol reduced heterodisulfide per min/mg membrane protein. Only protons are used as coupling ions for the generation of the electrochemical ion gradient. The membrane-bound F420H2:phenazine oxidoreductase complex (without the electron input module FpoF) probably catalyzes the oxidation of reduced ferredoxin and potentially acted as primary proton pump in this electron transport system
physiological function
heterodisulfide reductase (Hdr) is the valve that closes the cycle of methanogenesis, allowing energy to be conserved and providing an energetic advantage to the cell. Hdr catalyzes flavin-based electron bifurcation that results in the exergonic reduction of heterodisulfide (CoMS-S-CoB) coupled to the endergonic reduction of ferredoxin. In the proposed mechanism of bifurcation, the bifurcation-site flavin receives two electrons from a single donor, and then bifurcate one electron to reduce the heterodisulfide and one electron to reduce ferredoxin. Another round of bifurcation results in the complete reduction of CoM-S-S-CoB to HS-CoB and HS-CoM and 2 equivalents of reduced ferredoxin
physiological function
in the hydrogenotrophic methanogenic pathway, CO2 is reduced and then condensed to a C1-carrier methanofuran to form formyl-methanofuran. These reactions are catalyzed by the molybdenum-containing formyl-methanofuran dehydrogenase (EC 1.12.7.2), FmdABCDFG, or its tungsten isoform, FwdABCDFG. Electrons for CO2 reduction are provided by methyl viologen-reducing hydrogenase (MvhAG, EC 1.8.98.1) or formate dehydrogenase (FdhAB, EC 1.8.98.6) in complex with heterodisulfide reductase (HdrABC), which carries out flavin-based electron bifurcation (FBEB). In this process, the energy in a pair of electrons is split, giving rise to a strongly reducing electron for CO2 fixation and a weakly reducing electron for reduction of the heterodisulfide of coenzyme M and coenzyme B (CoM-S-S-CoB), a co-oxidant that is regenerated by the methane formation reaction. The electron transfer chain leads from formate via molybdopterin in FdhA to the FBEB-catalyzing HdrA. FdhB contains a partially solvent-exposed FAD molecule that forms a likely F420-binding site, which shows a fold similar to that of the FAD-containing site of F420-reducing hydrogenase (Frh). The electron transfer chains from FdhB FAD and the FdhA active site converge at an unpredicted [4Fe-4S] cluster with ligation from one histidine and three cysteine residues, and the [4Fe-4S] clusters in FdhAB form a conductive pathway with distances below 14 A
physiological function
reduction of the disulfide of coenzyme M and coenzyme B (CoMS-SCoB) by heterodisulfide reductases (HdrED and HdrABC) is the final step in all methanogenic pathways. Flavin-based electron bifurcation (FBEB) by soluble HdrABC homologues play additional roles in driving essential endergonic reactions at the expense of the exergonic reduction of CoMS-SCoM
physiological function
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the HdrABC-MvhAGD complex catalyzes an iron-sulfur cluster-assisted disulfide reduction reaction. This reaction is integrated into a flavin-based electron bifurcation (FBEB) process, a mode of energy coupling that optimizes the energy yield of the cell. The key subunits are HdrA, which carries the electron-bifurcating flavin adenine dinucleotide (FAD), and HdrB, which has been proposed to be the heterodisulfide reductase site
physiological function
the HdrABC-MvhAGD complex catalyzes an iron-sulfur cluster-assisted disulfide reduction reaction. This reaction is integrated into a flavin-based electron bifurcation (FBEB) process, a mode of energy coupling that optimizes the energy yield of the cell. The key subunits are HdrA, which carries the electron-bifurcating flavin adenine dinucleotide (FAD), and HdrB, which has been proposed to be the heterodisulfide reductase site
physiological function
P60200; Q58153; Q58273; Q58154; Q58274
the HdrABC-MvhAGD complex catalyzes an iron-sulfur cluster-assisted disulfide reduction reaction. This reaction is integrated into a flavin-based electron bifurcation (FBEB) process, a mode of energy coupling that optimizes the energy yield of the cell. The key subunits are HdrA, which carries the electron-bifurcating flavin adenine dinucleotide (FAD), and HdrB, which has been proposed to be the heterodisulfide reductase site
physiological function
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the HdrABC-MvhAGD complex catalyzes an iron-sulfur cluster-assisted disulfide reduction reaction. This reaction is integrated into a flavin-based electron bifurcation (FBEB) process, a mode of energy coupling that optimizes the energy yield of the cell. The key subunits are HdrA, which carries the electron-bifurcating flavin adenine dinucleotide (FAD), and HdrB, which has been proposed to be the heterodisulfide reductase site
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physiological function
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the HdrABC-MvhAGD complex catalyzes an iron-sulfur cluster-assisted disulfide reduction reaction. This reaction is integrated into a flavin-based electron bifurcation (FBEB) process, a mode of energy coupling that optimizes the energy yield of the cell. The key subunits are HdrA, which carries the electron-bifurcating flavin adenine dinucleotide (FAD), and HdrB, which has been proposed to be the heterodisulfide reductase site
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physiological function
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the HdrABC-MvhAGD complex catalyzes an iron-sulfur cluster-assisted disulfide reduction reaction. This reaction is integrated into a flavin-based electron bifurcation (FBEB) process, a mode of energy coupling that optimizes the energy yield of the cell. The key subunits are HdrA, which carries the electron-bifurcating flavin adenine dinucleotide (FAD), and HdrB, which has been proposed to be the heterodisulfide reductase site
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physiological function
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the HdrABC-MvhAGD complex catalyzes an iron-sulfur cluster-assisted disulfide reduction reaction. This reaction is integrated into a flavin-based electron bifurcation (FBEB) process, a mode of energy coupling that optimizes the energy yield of the cell. The key subunits are HdrA, which carries the electron-bifurcating flavin adenine dinucleotide (FAD), and HdrB, which has been proposed to be the heterodisulfide reductase site
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physiological function
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heterodisulfide reductase (Hdr) is the valve that closes the cycle of methanogenesis, allowing energy to be conserved and providing an energetic advantage to the cell. Hdr catalyzes flavin-based electron bifurcation that results in the exergonic reduction of heterodisulfide (CoMS-S-CoB) coupled to the endergonic reduction of ferredoxin. In the proposed mechanism of bifurcation, the bifurcation-site flavin receives two electrons from a single donor, and then bifurcate one electron to reduce the heterodisulfide and one electron to reduce ferredoxin. Another round of bifurcation results in the complete reduction of CoM-S-S-CoB to HS-CoB and HS-CoM and 2 equivalents of reduced ferredoxin
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physiological function
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reduction of the disulfide of coenzyme M and coenzyme B (CoMS-SCoB) by heterodisulfide reductases (HdrED and HdrABC) is the final step in all methanogenic pathways. Flavin-based electron bifurcation (FBEB) by soluble HdrABC homologues play additional roles in driving essential endergonic reactions at the expense of the exergonic reduction of CoMS-SCoM
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physiological function
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the HdrABC-MvhAGD complex catalyzes an iron-sulfur cluster-assisted disulfide reduction reaction. This reaction is integrated into a flavin-based electron bifurcation (FBEB) process, a mode of energy coupling that optimizes the energy yield of the cell. The key subunits are HdrA, which carries the electron-bifurcating flavin adenine dinucleotide (FAD), and HdrB, which has been proposed to be the heterodisulfide reductase site
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physiological function
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the HdrABC-MvhAGD complex catalyzes an iron-sulfur cluster-assisted disulfide reduction reaction. This reaction is integrated into a flavin-based electron bifurcation (FBEB) process, a mode of energy coupling that optimizes the energy yield of the cell. The key subunits are HdrA, which carries the electron-bifurcating flavin adenine dinucleotide (FAD), and HdrB, which has been proposed to be the heterodisulfide reductase site
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additional information
enzymological and structural characterizations of Fdh-Hdr-Fmd complexes from Methanospirillum hungatei. The complexes catalyze the reaction using electrons from formate and the reduced form of the electron carrier F420. Conformational changes in HdrA mediate electron bifurcation, and polyferredoxin FmdF directly transfers electrons to the CO2 reduction site, as evidenced by methanofuran-dependent flavin-based electron bifurcation even without free ferredoxin, a diffusible electron carrier between Hdr and Fmd. Conformational changes within the HdrA subunit provide a conformationally gated pathway for electrons to and from the bifurcating flavin adenine dinucleotide (FAD). The dimeric Fdh- Hdr-Fmd structure reveals that FdhAB and HdrABC are connected via MvhD and that a polyferredoxin FmdF bridges HdrABC and FmdABCDG. Tertiary and quartenary enzyme complex structures and structure-function analysis, detailed overview
additional information
the HdrABC subunits have different catalytic activities and contain the cofactors that comprise the electron-transferring conduits and heterodisulfide binding site, and facilitate the bifurcation of electrons from the sole flavin adenine dinucleotide (FAD) molecule in HdrA, see also EC 1.8.98.1, EC 1.8.98.4, and EC 1.8.98.5. The unusual noncubane iron-sulfur clusters are observed to bind and catalyze the reduction of CoM-S-S-CoB, and, based on crystal-soaking experiments with the disulfide, HS-CoB dissociates first after reduction from the first round of bifurcation. HS-CoM then dissociates after reduction from the second round of bifurcation. Structure-function relationship, overview
additional information
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the methanogenic heterodisulfide reductase (HdrABC-MvhAGD) uses two noncubane [4Fe-4S] clusters for reduction. Analysis of the structure of the native heterododecameric HdrABC-MvhAGD complex at 2.15 A resolution. Subunit HdrB of heterodisulfide reductase (HdrABC-MvhAGD) contains two noncubane [4Fe-4S] clusters tht are involved in reduction activity. The heterodisulfide is clamped between the two noncubane [4Fe-4S] clusters and homolytically cleaved, forming coenzyme M and B bound to each iron. Coenzymes are consecutively released upon one-by-one electron transfer. The HdrABC-MvhAGD atomic model serves as a structural template for numerous HdrABC homologs involved in diverse microbial metabolic pathways. The multisubunit enzyme complex is composed of a dimer of two HdrABC-MvhAGD heterohexamers with a flavin-containing HdrA dimer in the center, to which two catalytic arms, MvhAGD and HdrBC, are attached. MvhA and MvhG are homologous to the large and small subunits of [NiFe] hydrogenase (EC 1.12.7.2), respectively. The thioredoxin reductase domain of HdrA (145 to 236 and 315 to 567) resembles thioredoxin reductase in the fold and geometry of the FAD-binding site but forms a completely different dimer interface, owing to the perpendicular position of the respective two-fold axes. The thioredoxin-reductase domain of HdrA has, in addition, a [4Fe-4S] cluster (HA4) that is surrounded by several basic residues and coordinated with a Cys386, Cys399, Cys403, and Cys404 sequence motif (consensus sequence CX10-16-Y/W/H/F-C-S/A/C-X2-3CC). HdrB is unusual in that spectroscopic studies have suggested that disulfide reduction occurs through two one-electron steps rather than the typical two-electron step. HdrB contains a duplicated CCG motif with the sequence CX31-39CCX35-36CXXC. This motif is predicted to be a binding motif for iron-sulfur clusters, which occurs in numerous microbes. Structure comparisons
additional information
P60200; Q58153; Q58273; Q58154; Q58274
the methanogenic heterodisulfide reductase (HdrABC-MvhAGD) uses two noncubane [4Fe-4S] clusters for reduction. Analysis of the structure of the native heterododecameric HdrABC-MvhAGD complex at 2.15 A resolution. Subunit HdrB of heterodisulfide reductase (HdrABC-MvhAGD) contains two noncubane [4Fe-4S] clusters tht are involved in reduction activity. The heterodisulfide is clamped between the two noncubane [4Fe-4S] clusters and homolytically cleaved, forming coenzyme M and B bound to each iron. Coenzymes are consecutively released upon one-by-one electron transfer. The HdrABC-MvhAGD atomic model serves as a structural template for numerous HdrABC homologs involved in diverse microbial metabolic pathways. The multisubunit enzyme complex is composed of a dimer of two HdrABC-MvhAGD heterohexamers with a flavin-containing HdrA dimer in the center, to which two catalytic arms, MvhAGD and HdrBC, are attached. MvhA and MvhG are homologous to the large and small subunits of [NiFe] hydrogenase (EC 1.12.7.2), respectively. The thioredoxin reductase domain of HdrA (145 to 236 and 315 to 567) resembles thioredoxin reductase in the fold and geometry of the FAD-binding site but forms a completely different dimer interface, owing to the perpendicular position of the respective two-fold axes. The thioredoxin-reductase domain of HdrA has, in addition, a [4Fe-4S] cluster (HA4) that is surrounded by several basic residues and coordinated with a Cys386, Cys399, Cys403, and Cys404 sequence motif (consensus sequence CX10-16-Y/W/H/F-C-S/A/C-X2-3CC). HdrB is unusual in that spectroscopic studies have suggested that disulfide reduction occurs through two one-electron steps rather than the typical two-electron step. HdrB contains a duplicated CCG motif with the sequence CX31-39CCX35-36CXXC. This motif is predicted to be a binding motif for iron-sulfur clusters, which occurs in numerous microbes. Structure comparisons
additional information
the methanogenic heterodisulfide reductase (HdrABC-MvhAGD) uses two noncubane [4Fe-4S] clusters for reduction. Analysis of the structure of the native heterododecameric HdrABC-MvhAGD complex at 2.15 A resolution. Subunit HdrB of heterodisulfide reductase (HdrABC-MvhAGD) contains two noncubane [4Fe-4S] clusters tht are involved in reduction activity. The heterodisulfide is clamped between the two noncubane [4Fe-4S] clusters and homolytically cleaved, forming coenzyme M and B bound to each iron. Coenzymes are consecutively released upon one-by-one electron transfer. The HdrABC-MvhAGD atomic model serves as a structural template for numerous HdrABC homologs involved in diverse microbial metabolic pathways. The multisubunit enzyme complex is composed of a dimer of two HdrABC-MvhAGD heterohexamers with a flavin-containing HdrA dimer in the center, to which two catalytic arms, MvhAGD and HdrBC, are attached. MvhA and MvhG are homologous to the large and small subunits of [NiFe] hydrogenase (EC 1.12.7.2), respectively. The thioredoxin reductase domain of HdrA (145 to 236 and 315 to 567) resembles thioredoxin reductase in the fold and geometry of the FAD-binding site but forms a completely different dimer interface, owing to the perpendicular position of the respective two-fold axes. The thioredoxin-reductase domain of HdrA has, in addition, a [4Fe-4S] cluster (HA4) that is surrounded by several basic residues and coordinated with a Cys386, Cys399, Cys403, and Cys404 sequence motif (consensus sequence CX10-16-Y/W/H/F-C-S/A/C-X2-3CC). HdrB is unusual in that spectroscopic studies have suggested that disulfide reduction occurs through two one-electron steps rather than the typical two-electron step. HdrB contains a duplicated CCG motif with the sequence CX31-39CCX35-36CXXC. This motif is predicted to be a binding motif for iron-sulfur clusters, which occurs in numerous microbes. Structure comparisons. Structure-function anaysis, detailed overview
additional information
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the methanogenic heterodisulfide reductase (HdrABC-MvhAGD) uses two noncubane [4Fe-4S] clusters for reduction. Analysis of the structure of the native heterododecameric HdrABC-MvhAGD complex at 2.15 A resolution. Subunit HdrB of heterodisulfide reductase (HdrABC-MvhAGD) contains two noncubane [4Fe-4S] clusters tht are involved in reduction activity. The heterodisulfide is clamped between the two noncubane [4Fe-4S] clusters and homolytically cleaved, forming coenzyme M and B bound to each iron. Coenzymes are consecutively released upon one-by-one electron transfer. The HdrABC-MvhAGD atomic model serves as a structural template for numerous HdrABC homologs involved in diverse microbial metabolic pathways. The multisubunit enzyme complex is composed of a dimer of two HdrABC-MvhAGD heterohexamers with a flavin-containing HdrA dimer in the center, to which two catalytic arms, MvhAGD and HdrBC, are attached. MvhA and MvhG are homologous to the large and small subunits of [NiFe] hydrogenase (EC 1.12.7.2), respectively. The thioredoxin reductase domain of HdrA (145 to 236 and 315 to 567) resembles thioredoxin reductase in the fold and geometry of the FAD-binding site but forms a completely different dimer interface, owing to the perpendicular position of the respective two-fold axes. The thioredoxin-reductase domain of HdrA has, in addition, a [4Fe-4S] cluster (HA4) that is surrounded by several basic residues and coordinated with a Cys386, Cys399, Cys403, and Cys404 sequence motif (consensus sequence CX10-16-Y/W/H/F-C-S/A/C-X2-3CC). HdrB is unusual in that spectroscopic studies have suggested that disulfide reduction occurs through two one-electron steps rather than the typical two-electron step. HdrB contains a duplicated CCG motif with the sequence CX31-39CCX35-36CXXC. This motif is predicted to be a binding motif for iron-sulfur clusters, which occurs in numerous microbes. Structure comparisons
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additional information
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the methanogenic heterodisulfide reductase (HdrABC-MvhAGD) uses two noncubane [4Fe-4S] clusters for reduction. Analysis of the structure of the native heterododecameric HdrABC-MvhAGD complex at 2.15 A resolution. Subunit HdrB of heterodisulfide reductase (HdrABC-MvhAGD) contains two noncubane [4Fe-4S] clusters tht are involved in reduction activity. The heterodisulfide is clamped between the two noncubane [4Fe-4S] clusters and homolytically cleaved, forming coenzyme M and B bound to each iron. Coenzymes are consecutively released upon one-by-one electron transfer. The HdrABC-MvhAGD atomic model serves as a structural template for numerous HdrABC homologs involved in diverse microbial metabolic pathways. The multisubunit enzyme complex is composed of a dimer of two HdrABC-MvhAGD heterohexamers with a flavin-containing HdrA dimer in the center, to which two catalytic arms, MvhAGD and HdrBC, are attached. MvhA and MvhG are homologous to the large and small subunits of [NiFe] hydrogenase (EC 1.12.7.2), respectively. The thioredoxin reductase domain of HdrA (145 to 236 and 315 to 567) resembles thioredoxin reductase in the fold and geometry of the FAD-binding site but forms a completely different dimer interface, owing to the perpendicular position of the respective two-fold axes. The thioredoxin-reductase domain of HdrA has, in addition, a [4Fe-4S] cluster (HA4) that is surrounded by several basic residues and coordinated with a Cys386, Cys399, Cys403, and Cys404 sequence motif (consensus sequence CX10-16-Y/W/H/F-C-S/A/C-X2-3CC). HdrB is unusual in that spectroscopic studies have suggested that disulfide reduction occurs through two one-electron steps rather than the typical two-electron step. HdrB contains a duplicated CCG motif with the sequence CX31-39CCX35-36CXXC. This motif is predicted to be a binding motif for iron-sulfur clusters, which occurs in numerous microbes. Structure comparisons
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additional information
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the methanogenic heterodisulfide reductase (HdrABC-MvhAGD) uses two noncubane [4Fe-4S] clusters for reduction. Analysis of the structure of the native heterododecameric HdrABC-MvhAGD complex at 2.15 A resolution. Subunit HdrB of heterodisulfide reductase (HdrABC-MvhAGD) contains two noncubane [4Fe-4S] clusters tht are involved in reduction activity. The heterodisulfide is clamped between the two noncubane [4Fe-4S] clusters and homolytically cleaved, forming coenzyme M and B bound to each iron. Coenzymes are consecutively released upon one-by-one electron transfer. The HdrABC-MvhAGD atomic model serves as a structural template for numerous HdrABC homologs involved in diverse microbial metabolic pathways. The multisubunit enzyme complex is composed of a dimer of two HdrABC-MvhAGD heterohexamers with a flavin-containing HdrA dimer in the center, to which two catalytic arms, MvhAGD and HdrBC, are attached. MvhA and MvhG are homologous to the large and small subunits of [NiFe] hydrogenase (EC 1.12.7.2), respectively. The thioredoxin reductase domain of HdrA (145 to 236 and 315 to 567) resembles thioredoxin reductase in the fold and geometry of the FAD-binding site but forms a completely different dimer interface, owing to the perpendicular position of the respective two-fold axes. The thioredoxin-reductase domain of HdrA has, in addition, a [4Fe-4S] cluster (HA4) that is surrounded by several basic residues and coordinated with a Cys386, Cys399, Cys403, and Cys404 sequence motif (consensus sequence CX10-16-Y/W/H/F-C-S/A/C-X2-3CC). HdrB is unusual in that spectroscopic studies have suggested that disulfide reduction occurs through two one-electron steps rather than the typical two-electron step. HdrB contains a duplicated CCG motif with the sequence CX31-39CCX35-36CXXC. This motif is predicted to be a binding motif for iron-sulfur clusters, which occurs in numerous microbes. Structure comparisons
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additional information
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the methanogenic heterodisulfide reductase (HdrABC-MvhAGD) uses two noncubane [4Fe-4S] clusters for reduction. Analysis of the structure of the native heterododecameric HdrABC-MvhAGD complex at 2.15 A resolution. Subunit HdrB of heterodisulfide reductase (HdrABC-MvhAGD) contains two noncubane [4Fe-4S] clusters tht are involved in reduction activity. The heterodisulfide is clamped between the two noncubane [4Fe-4S] clusters and homolytically cleaved, forming coenzyme M and B bound to each iron. Coenzymes are consecutively released upon one-by-one electron transfer. The HdrABC-MvhAGD atomic model serves as a structural template for numerous HdrABC homologs involved in diverse microbial metabolic pathways. The multisubunit enzyme complex is composed of a dimer of two HdrABC-MvhAGD heterohexamers with a flavin-containing HdrA dimer in the center, to which two catalytic arms, MvhAGD and HdrBC, are attached. MvhA and MvhG are homologous to the large and small subunits of [NiFe] hydrogenase (EC 1.12.7.2), respectively. The thioredoxin reductase domain of HdrA (145 to 236 and 315 to 567) resembles thioredoxin reductase in the fold and geometry of the FAD-binding site but forms a completely different dimer interface, owing to the perpendicular position of the respective two-fold axes. The thioredoxin-reductase domain of HdrA has, in addition, a [4Fe-4S] cluster (HA4) that is surrounded by several basic residues and coordinated with a Cys386, Cys399, Cys403, and Cys404 sequence motif (consensus sequence CX10-16-Y/W/H/F-C-S/A/C-X2-3CC). HdrB is unusual in that spectroscopic studies have suggested that disulfide reduction occurs through two one-electron steps rather than the typical two-electron step. HdrB contains a duplicated CCG motif with the sequence CX31-39CCX35-36CXXC. This motif is predicted to be a binding motif for iron-sulfur clusters, which occurs in numerous microbes. Structure comparisons
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additional information
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the HdrABC subunits have different catalytic activities and contain the cofactors that comprise the electron-transferring conduits and heterodisulfide binding site, and facilitate the bifurcation of electrons from the sole flavin adenine dinucleotide (FAD) molecule in HdrA, see also EC 1.8.98.1, EC 1.8.98.4, and EC 1.8.98.5. The unusual noncubane iron-sulfur clusters are observed to bind and catalyze the reduction of CoM-S-S-CoB, and, based on crystal-soaking experiments with the disulfide, HS-CoB dissociates first after reduction from the first round of bifurcation. HS-CoM then dissociates after reduction from the second round of bifurcation. Structure-function relationship, overview
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additional information
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the methanogenic heterodisulfide reductase (HdrABC-MvhAGD) uses two noncubane [4Fe-4S] clusters for reduction. Analysis of the structure of the native heterododecameric HdrABC-MvhAGD complex at 2.15 A resolution. Subunit HdrB of heterodisulfide reductase (HdrABC-MvhAGD) contains two noncubane [4Fe-4S] clusters tht are involved in reduction activity. The heterodisulfide is clamped between the two noncubane [4Fe-4S] clusters and homolytically cleaved, forming coenzyme M and B bound to each iron. Coenzymes are consecutively released upon one-by-one electron transfer. The HdrABC-MvhAGD atomic model serves as a structural template for numerous HdrABC homologs involved in diverse microbial metabolic pathways. The multisubunit enzyme complex is composed of a dimer of two HdrABC-MvhAGD heterohexamers with a flavin-containing HdrA dimer in the center, to which two catalytic arms, MvhAGD and HdrBC, are attached. MvhA and MvhG are homologous to the large and small subunits of [NiFe] hydrogenase (EC 1.12.7.2), respectively. The thioredoxin reductase domain of HdrA (145 to 236 and 315 to 567) resembles thioredoxin reductase in the fold and geometry of the FAD-binding site but forms a completely different dimer interface, owing to the perpendicular position of the respective two-fold axes. The thioredoxin-reductase domain of HdrA has, in addition, a [4Fe-4S] cluster (HA4) that is surrounded by several basic residues and coordinated with a Cys386, Cys399, Cys403, and Cys404 sequence motif (consensus sequence CX10-16-Y/W/H/F-C-S/A/C-X2-3CC). HdrB is unusual in that spectroscopic studies have suggested that disulfide reduction occurs through two one-electron steps rather than the typical two-electron step. HdrB contains a duplicated CCG motif with the sequence CX31-39CCX35-36CXXC. This motif is predicted to be a binding motif for iron-sulfur clusters, which occurs in numerous microbes. Structure comparisons. Structure-function anaysis, detailed overview
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additional information
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the methanogenic heterodisulfide reductase (HdrABC-MvhAGD) uses two noncubane [4Fe-4S] clusters for reduction. Analysis of the structure of the native heterododecameric HdrABC-MvhAGD complex at 2.15 A resolution. Subunit HdrB of heterodisulfide reductase (HdrABC-MvhAGD) contains two noncubane [4Fe-4S] clusters tht are involved in reduction activity. The heterodisulfide is clamped between the two noncubane [4Fe-4S] clusters and homolytically cleaved, forming coenzyme M and B bound to each iron. Coenzymes are consecutively released upon one-by-one electron transfer. The HdrABC-MvhAGD atomic model serves as a structural template for numerous HdrABC homologs involved in diverse microbial metabolic pathways. The multisubunit enzyme complex is composed of a dimer of two HdrABC-MvhAGD heterohexamers with a flavin-containing HdrA dimer in the center, to which two catalytic arms, MvhAGD and HdrBC, are attached. MvhA and MvhG are homologous to the large and small subunits of [NiFe] hydrogenase (EC 1.12.7.2), respectively. The thioredoxin reductase domain of HdrA (145 to 236 and 315 to 567) resembles thioredoxin reductase in the fold and geometry of the FAD-binding site but forms a completely different dimer interface, owing to the perpendicular position of the respective two-fold axes. The thioredoxin-reductase domain of HdrA has, in addition, a [4Fe-4S] cluster (HA4) that is surrounded by several basic residues and coordinated with a Cys386, Cys399, Cys403, and Cys404 sequence motif (consensus sequence CX10-16-Y/W/H/F-C-S/A/C-X2-3CC). HdrB is unusual in that spectroscopic studies have suggested that disulfide reduction occurs through two one-electron steps rather than the typical two-electron step. HdrB contains a duplicated CCG motif with the sequence CX31-39CCX35-36CXXC. This motif is predicted to be a binding motif for iron-sulfur clusters, which occurs in numerous microbes. Structure comparisons
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x * 18000, subunit HdrC2, SDS-PAGE
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x * 33000, subunit HdrB2, SDS-PAGE
oligomer
P60200; Q58153; Q58273; Q58154; Q58274
structure analysis of the native heterododecameric HdrABC-MvhAGD complex, overview. The multisubunit enzyme complex is composed of a dimer of two HdrABC-MvhAGD heterohexamers with a flavin-containing HdrA dimer in the center, to which two catalytic arms, MvhAGD and HdrBC, are attached
oligomer
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structure analysis of the native heterododecameric HdrABC-MvhAGD complex, overview. The multisubunit enzyme complex is composed of a dimer of two HdrABC-MvhAGD heterohexamers with a flavin-containing HdrA dimer in the center, to which two catalytic arms, MvhAGD and HdrBC, are attached
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oligomer
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structure analysis of the native heterododecameric HdrABC-MvhAGD complex, overview. The multisubunit enzyme complex is composed of a dimer of two HdrABC-MvhAGD heterohexamers with a flavin-containing HdrA dimer in the center, to which two catalytic arms, MvhAGD and HdrBC, are attached
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oligomer
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structure analysis of the native heterododecameric HdrABC-MvhAGD complex, overview. The multisubunit enzyme complex is composed of a dimer of two HdrABC-MvhAGD heterohexamers with a flavin-containing HdrA dimer in the center, to which two catalytic arms, MvhAGD and HdrBC, are attached
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oligomer
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structure analysis of the native heterododecameric HdrABC-MvhAGD complex, overview. The multisubunit enzyme complex is composed of a dimer of two HdrABC-MvhAGD heterohexamers with a flavin-containing HdrA dimer in the center, to which two catalytic arms, MvhAGD and HdrBC, are attached
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oligomer
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structure analysis of the native heterododecameric HdrABC-MvhAGD complex, overview. The multisubunit enzyme complex is composed of a dimer of two HdrABC-MvhAGD heterohexamers with a flavin-containing HdrA dimer in the center, to which two catalytic arms, MvhAGD and HdrBC, are attached
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oligomer
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the multisubunit enzyme complex is composed of a dimer of two HdrABC-MvhAGD heterohexamers with a flavin-containing HdrA dimer in the center, to which two catalytic arms, MvhAGD and HdrBC, are attached
oligomer
structure analysis of the native heterododecameric HdrABC-MvhAGD complex, overview. The multisubunit enzyme complex is composed of a dimer of two HdrABC-MvhAGD heterohexamers with a flavin-containing HdrA dimer in the center, to which two catalytic arms, MvhAGD and HdrBC, are attached. HdrA is tightly associated with HdrA' (amino acid residues of the partner protomer are marked with an apostrophe) and comprises anN-terminal (1 to 133), a thioredoxin-reductase (145 to 236 and 315 to 567), an inserted ferredoxin (237 to 314), and a C-terminal ferredoxin domain (568 to 654)
oligomer
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structure analysis of the native heterododecameric HdrABC-MvhAGD complex, overview. The multisubunit enzyme complex is composed of a dimer of two HdrABC-MvhAGD heterohexamers with a flavin-containing HdrA dimer in the center, to which two catalytic arms, MvhAGD and HdrBC, are attached. HdrA is tightly associated with HdrA' (amino acid residues of the partner protomer are marked with an apostrophe) and comprises anN-terminal (1 to 133), a thioredoxin-reductase (145 to 236 and 315 to 567), an inserted ferredoxin (237 to 314), and a C-terminal ferredoxin domain (568 to 654)
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additional information
three-dimensional map and model of the dimeric Fdh-Hdr-Fmd complex, its active sites, and Fe-S cluster relay. The structure of the D3-hexameric complex is made by threefold repetition of the dimeric structure, and contains dimeric organization of Hdr and Fmd subunits. Mass spectrometry reveals that the Fdh-Hdr-Fmd complex elutes from gel filtration primarily as a 1-MDa dimer of subunits FdhAB-MvhD-HdrABCFmdABCDFG. The Fdh-Hdr complexes are isolated as two oligomeric states, which contain FdhAB-MvhD-HdrABCFmdF. Two of five isoenzymes of FdhA and are detected in all complexes
additional information
the HdrABC subunits have different catalytic activities and contain the cofactors that comprise the electron-transferring conduits and heterodisulfide binding site, and facilitate the bifurcation of electrons from the sole flavin adenine dinucleotide (FAD) molecule in HdrA
additional information
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the HdrABC subunits have different catalytic activities and contain the cofactors that comprise the electron-transferring conduits and heterodisulfide binding site, and facilitate the bifurcation of electrons from the sole flavin adenine dinucleotide (FAD) molecule in HdrA
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Ramos, A.R.; Grein, F.; Oliveira, G.P.; Venceslau, S.S.; Keller, K.L.; Wall, J.D.; Pereira, I.A.
The FlxABCD-HdrABC proteins correspond to a novel NADH dehydrogenase/heterodisulfide reductase widespread in anaerobic bacteria and involved in ethanol metabolism in Desulfovibrio vulgaris Hildenborough
Environ. Microbiol.
17
2288-2305
2015
Desulfovibrio vulgaris, Desulfovibrio vulgaris ATCC 29579
brenda
Kroeninger, L.; Berger, S.; Welte, C.; Deppenmeier, U.
Evidence for the involvement of two heterodisulfide reductases in the energy-conserving system of Methanomassiliicoccus luminyensis
FEBS J.
283
472-483
2016
Methanomassiliicoccus luminyensis, Methanomassiliicoccus luminyensis DSM 25720
brenda
Yan, Z.; Wang, M.; Ferry, J.G.
A ferredoxin- and F420H2-dependent, electron-bifurcating, heterodisulfide reductase with homologs in the domains Bacteria and Archaea
mBio
8
e02285-16
2017
Methanosarcina acetivorans
brenda
Hamann, N.; Mander, G.J.; Shokes, J.E.; Scott, R.A.; Bennati, M.; Hedderich, R.
A cysteine-rich CCG domain contains a novel [4Fe-4S] cluster binding motif as deduced from studies with subunit B of heterodisulfide reductase from Methanothermobacter marburgensis
Biochemistry
46
12875-12885
2007
Methanothermobacter marburgensis (Q50755)
brenda
Mangold, S.; Valdes, J.; Holmes, D.S.; Dopson, M.
Sulfur metabolism in the extreme acidophile Acidithiobacillus caldus
Front. Microbiol.
10
17
2011
Acidithiobacillus caldus
brenda
Fielding, A.J.; Parey, K.; Ermler, U.; Scheller, S.; Jaun, B.; Bennati, M.
Advanced electron paramagnetic resonance on the catalytic iron-sulfur cluster bound to the CCG domain of heterodisulfide reductase and succinate quinone reductase
J. Biol. Inorg. Chem.
18
905-915
2013
Methanothermobacter marburgensis
brenda
Buan, N.R.; Metcalf, W.W.
Methanogenesis by Methanosarcina acetivorans involves two structurally and functionally distinct classes of heterodisulfide reductase
Mol. Microbiol.
75
843-853
2010
Methanosarcina acetivorans
brenda
Lubner, C.E.; Peters, J.W.
Electron bifurcation makes the puzzle pieces fall energetically into place in methanogenic energy conservation
ChemBioChem
18
2295-2297
2017
Methanothermococcus thermolithotrophicus (A0A2D0TCB9), Methanothermococcus thermolithotrophicus DSM 2095 (A0A2D0TCB9)
brenda
Kroeninger, L.; Steiniger, F.; Berger, S.; Kraus, S.; Welte, C.U.; Deppenmeier, U.
Energy conservation in the gut microbe Methanomassiliicoccus luminyensis is based on membrane-bound ferredoxin oxidation coupled to heterodisulfide reduction
FEBS J.
286
3831-3843
2019
Methanomassiliicoccus luminyensis
brenda
Yan, Z.; Ferry, J.
Electron bifurcation and confurcation in methanogenesis and reverse methanogenesis
Front. Microbiol.
9
1322
2018
Methanothermococcus thermolithotrophicus (A0A2D0TCB9 AND A0A2D0TCB4 AND A0A2D0TC97), Methanothermococcus thermolithotrophicus DSM 2095 (A0A2D0TCB9 AND A0A2D0TCB4 AND A0A2D0TC97)
brenda
Wagner, T.; Koch, J.; Ermler, U.; Shima, S.
Methanogenic heterodisulfide reductase (HdrABC-MvhAGD) uses two noncubane [4Fe-4S] clusters for reduction
Science
357
699-703
2017
Methanothermobacter wolfeii, Methanothermococcus thermolithotrophicus (A0A2D0TCB9 AND A0A2D0TCB4 AND A0A2D0TC97), Methanocaldococcus jannaschii (P60200 AND Q58153 AND Q58273 AND Q58154 AND Q58274), Methanocaldococcus jannaschii NBRC 100440 (P60200 AND Q58153 AND Q58273 AND Q58154 AND Q58274), Methanocaldococcus jannaschii DSM 2661 (P60200 AND Q58153 AND Q58273 AND Q58154 AND Q58274), Methanocaldococcus jannaschii ATCC 43067 (P60200 AND Q58153 AND Q58273 AND Q58154 AND Q58274), Methanocaldococcus jannaschii JAL-1 (P60200 AND Q58153 AND Q58273 AND Q58154 AND Q58274), Methanothermococcus thermolithotrophicus DSM 2095 (A0A2D0TCB9 AND A0A2D0TCB4 AND A0A2D0TC97), Methanocaldococcus jannaschii JCM 10045 (P60200 AND Q58153 AND Q58273 AND Q58154 AND Q58274)
brenda
Watanabe, T.; Pfeil-Gardiner, O.; Kahnt, J.; Koch, J.; Shima, S.; Murphy, B.
Three-megadalton complex of methanogenic electron-bifurcating and CO2-fixing enzymes
Science
373
1151-1156
2021
Methanospirillum hungatei (Q2FKZ1)
brenda