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Information on EC 2.8.4.1 - coenzyme-B sulfoethylthiotransferase and Organism(s) Methanothermobacter marburgensis and UniProt Accession P11560
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2.8.4.1 coenzyme-B sulfoethylthiotransferaseIUBMB Comments
This enzyme catalyses the final step in methanogenesis, the biological production of methane. This important anaerobic process is carried out only by methanogenic archaea. The enzyme can also function in reverse, for anaerobic oxidation of methane.The enzyme requires the hydroporphinoid nickel complex coenzyme F430. Highly specific for coenzyme B with a heptanoyl chain; ethyl CoM and difluoromethyl CoM are poor substrates. The sulfide sulfur can be replaced by selenium but not by oxygen.
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Word Map
- 2.8.4.1
-
methanogen
- methane
- archaea
-
methanogenesis
- nickel
- methanobacterium
- methanosarcina
-
methanotrophic
-
hydrogenotrophic
- thermoautotrophicum
- ch4
- methanosarcinales
- methanomicrobiales
- methanothermobacter
-
sulfate-reducing
- heterodisulfide
- methanobrevibacter
-
methane-producing
-
seep
- acetivorans
-
anme-1
-
t-rflp
- methanobacteriales
-
biogas
-
phylotypes
- methanosarcinaceae
-
nickel-containing
-
acetoclastic
- methanosaeta
- marburgensis
-
methane-oxidizing
-
syntrophic
-
methane-forming
- 2-bromoethanesulfonate
- biofuel production
- analysis
- vannielii
- methanoculleus
-
niiii
- methanopyrus
- synthesis
- methanococcales
- hs-com
- environmental protection
- com-s-s-cob
The taxonomic range for the selected organisms is: Methanothermobacter marburgensis
The expected taxonomic range for this enzyme is: Archaea, Eukaryota, Bacteria
The expected taxonomic range for this enzyme is: Archaea, Eukaryota, Bacteria
Synonyms
methyl-coenzyme m reductase, methyl coenzyme m reductase, methyl-com reductase, methyl coenzyme-m reductase, mcr ii, mcr i, mcrox1, methyl coenzyme m reductase a, methyl-coenzyme-m reductase, methyl-coenzyme m reductase a, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
2-(methylthio)ethanesulfonic acid reductase
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-
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Coenzyme-B sulfoethylthiotransferase alpha
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-
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Coenzyme-B sulfoethylthiotransferase beta
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Coenzyme-B sulfoethylthiotransferase gamma
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-
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MCR
MCR I alpha
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-
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MCR I beta
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-
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MCR I gamma
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-
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MCR II alpha
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-
-
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MCR II beta
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-
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MCR II gamma
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-
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methyl coenzyme M reductase
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methyl-coenzyme M reductase
methyl-CoM reductase
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methyl-ScoM reductase
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S-methyl-coenzyme M reductase
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MCR
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methyl-coenzyme M reductase
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
methyl-CoM + CoB = CoM-S-S-CoB + methane
in the active site region of both isozymes, five modified amino acids occur determined by mass spectrometry: thioglycine alpha445, forming a thioxo peptide/thioamide bond with tyrosine alpha446, S-methylcysteine alpha452, 2-(S)-methylglutamine alpha400, 1-N-methylhistidine alpha257 and 5-(S)-methylarginine alpha271
-
methyl-CoM + CoB = CoM-S-S-CoB + methane
mechanism, nucleophilic attack of Ni(I)-MCRred1 on the methyl group of methyl-SCoM generates a methyl-Ni intermediate
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methyl-CoM + CoB = CoM-S-S-CoB + methane
two possible catalytic mechanisms, overview
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methyl-CoM + CoB = CoM-S-S-CoB + methane
reaction mechanism, different varaints, the Ni(I) center is assumed to attack the thioether sulfur of CH3-S-CoM, generating -CH3 and the thiolate complex CoM-SNi(II)F430 as intermediates, detailed overview
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methyl-CoM + CoB = CoM-S-S-CoB + methane
Two reaction mechanisms for methane formation distinguishable by the first step of catalysis, overview
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methyl-CoM + CoB = CoM-S-S-CoB + methane
catalytic mechanism, the first step of the mechanism is proposed to involve a nucleophilic attack of the NiI active state, MCRred1, on Me-SCoM to form a NiIII-methyl intermediate, spectroscopic analysis and structures, overview
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methyl-CoM + CoB = CoM-S-S-CoB + methane
the first step of the mechanism is proposed to involve a nucleophilic attack of the NiI active state, MCRred1, on Me-SCoM to form a NiIII-methyl intermediate, spectroscopic analysis and structures, overview
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methyl-CoM + CoB = CoM-S-S-CoB + methane
radical mechanism of biological methane synthesis by methyl-coenzyme M reductase, overview. Transient kinetic, spectroscopic [ultraviolet-visible (UV-Vis), EPR, and MCD], and computational studies of the first step in the MCR catalytic mechanism are performed to trap and identify the key intermediates that differ between proposed mechanisms I and II
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
sulfo ethyl group transfer
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PATHWAY SOURCE
PATHWAYS
BRENDA
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SYSTEMATIC NAME
IUBMB Comments
methyl-CoM:CoB S-(2-sulfoethyl)thiotransferase
This enzyme catalyses the final step in methanogenesis, the biological production of methane. This important anaerobic process is carried out only by methanogenic archaea. The enzyme can also function in reverse, for anaerobic oxidation of methane.The enzyme requires the hydroporphinoid nickel complex coenzyme F430. Highly specific for coenzyme B with a heptanoyl chain; ethyl CoM and difluoromethyl CoM are poor substrates. The sulfide sulfur can be replaced by selenium but not by oxygen.
CAS REGISTRY NUMBER
COMMENTARY
53060-41-6
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
2-(methylthio)ethanesulfonate + N-(7-mercaptoheptanoyl)threonine 3-O-phosphate
CoM-S-S-CoB + methane
2-(methylthio)ethansulfonate + N-(7-mercaptoheptanoyl)threonine 3-O-phosphate
CoM-S-S-CoB + methane
-
i.e. CoM and CoB
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-
?
CH3-S-CoM + HS-CoB6
CoM-S-S-CoB6 + methane
-
i.e. N-7-mercaptohexanoylthreonine phosphate
-
-
?
CH3-S-CoM + HS-CoB8
CoM-S-S-CoB8 + methane
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a two-electron transfer reaction
-
-
?
CH3-S-CoM + SH-CoB8
CoM-S-S-CoB8 + methane
i.e. N-8-mercaptooctanoylthreonine phosphate
-
-
?
CH3-S-CoM + SH-CoB9
CoM-S-S-CoB9 + methane
i.e. N-9-mercaptononanoylthreonine phosphate
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-
?
ethyl coenzyme M + coenzyme B
ethane + CoM-S-S-CoB
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1% of the activity with methyl coenzyme M
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-
?
methyl-coenzyme M + N-(7-mercaptoheptanoyl)threonine 3-O-phosphate (coenzyme B)
methane + CoB-S-S-CoM
-
i.e. methyl-SCoM
a the mixed disulfide
-
?
methyl-coenzyme M + N-(7-mercaptoheptanoyl)threonine 3-O-phosphate (coenzyme B)
methane + CoM-S-S-CoB
methylmercaptopropionate + HS-CoB
?
-
is about 110fold less reactive than the natural substrate methyl-SCoM
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-
?
2-(methylthio)ethanesulfonate + N-(7-mercaptoheptanoyl)threonine 3-O-phosphate
CoM-S-S-CoB + methane
-
i.e. CoM and CoB
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-
?
2-(methylthio)ethanesulfonate + N-(7-mercaptoheptanoyl)threonine 3-O-phosphate
CoM-S-S-CoB + methane
-
i.e. CoM and CoB, the enzyme exists in the the inactive Ni(II) MCRox1-silent form and the active Ni(I) MCRred1 form with transition from MCRred1 to MCRred2 forms, the protein is able to undergo a conformational change upon binding of the second substrate. Analysis of the catalytic mechanism of the reduction at the nickel center using inhibitory fluorescent trifluoromethyl thio esters of the substrate CoB for spectroscopic analysis of the structure of the enzyme-cofactor complex, derivatives synthesis, overview
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-
?
CH3-S-CoM + HS-CoB
CoM-S-S-CoB + methane
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i.e. methyl-coenzyme M + coenzyme B
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?
CH3-S-CoM + HS-CoB
CoM-S-S-CoB + methane
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key step in the convertion of C1 substrates or acetate to methane thereby providing energy for the cell
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?
CH3-S-CoM + HS-CoB
CoM-S-S-CoB + methane
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MCR catalyzes the first proposed step in anaerobic methane oxidation and terminal step in methanogenesis by using N-7-mercaptoheptanolyl-threonine phosphate, i.e. CoB-SH. as the two-electron donor to reduce 2-(methylthiol)-ethane sulfonate, i.e. methyl-SCoM, to methane, and producing the heterodisulfide, CoBS-SCoM
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-
?
CH3-S-CoM + HS-CoB
CoM-S-S-CoB + methane
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MCR catalyzes the methane-forming step in methanogenic archaea
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-
?
CH3-S-CoM + HS-CoB
CoM-S-S-CoB + methane
-
catalytic cycle and proton transfer mechanism and energetics, reaction complex formations and mechanism, detailed overview
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-
?
CH3-S-CoM + HS-CoB
CoM-S-S-CoB + methane
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i.e. methyl-coenzyme M + coenzyme B, selectivity of the MCR reaction toward nucleophilic attack by Ni(I)
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-
?
CH3-S-CoM + HS-CoB
CoM-S-S-CoB + methane
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i.e. methyl-coenzyme M or 2-methylmercaptoethanesulfonate + coenzyme B or N-7-mercaptoheptanoylthreonine phosphate
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?
CH3-S-CoM + HS-CoB
CoM-S-S-CoB + methane
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MCR contains a thioxo peptide bond and methylated amino acids in the active site region, the number of methylated amino acids varies between species, overview
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?
CH3-S-CoM + HS-CoB
CoM-S-S-CoB + methane
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the active enzyme is in the MCRred1c form, coordinated ligands of the two paramagnetic MCRred2 states, reduction and oxidation states and critical bond activation step, detailed overview
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?
CH3-S-CoM + HS-CoB
CoM-S-S-CoB + methane
HS-CoB is N-(7-mercaptoheptanoyl)-L-threonine 3-O-phosphate
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-
?
CH3-S-CoM + HS-CoB
CoM-S-S-CoB + methane
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i.e. N-7-mercaptoheptanoylthreonine phosphate, Ni(III)-methyl is an intermediate in methane formation
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-
?
CH3-S-CoM + SH-CoB5
CoM-S-S-CoB5 + methane
i.e. N-5-mercaptopentanoylthreonine phosphate
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-
?
CH3-S-CoM + SH-CoB6
CoM-S-S-CoB6 + methane
i.e. N-6-mercaptohexanoylthreonine phosphate, slow substrate
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?
CH3-S-CoM + SH-CoB6
CoM-S-S-CoB6 + methane
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methanogenesis occurs 1000fold more slowly than with SH-CoB
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-
?
methyl coenzyme M + coenzyme B
methane + CoM-S-S-CoB
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-
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?
methyl coenzyme M + coenzyme B
methane + CoM-S-S-CoB
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discussion of mechanism
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?
methyl-coenzyme M + coenzyme B
methane + CoM-S-S-CoB
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-
-
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?
methyl-coenzyme M + coenzyme B
methane + CoM-S-S-CoB
-
spin density and coenzyme M coordination geometry of the ox1 form of methyl-coenzyme M reductase
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-
?
methyl-coenzyme M + N-(7-mercaptoheptanoyl)threonine 3-O-phosphate (coenzyme B)
methane + CoM-S-S-CoB
-
i.e. methyl-SCoM
a the mixed disulfide
-
?
methyl-coenzyme M + N-(7-mercaptoheptanoyl)threonine 3-O-phosphate (coenzyme B)
methane + CoM-S-S-CoB
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the enzyme catalyzes the methane forming step in methane biosynthesis by methanogenic archaea
a the mixed disulfide
-
?
methyl-CoM + CoB
CoM-S-S-CoB + methane
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-
-
?
additional information
?
-
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MCR also appears to initiate anaerobic methane oxidation, the reverse methanogenesis
-
-
?
additional information
?
-
-
the enzyme catalyzes the final step in methane biosynthesis by methanogenic archaea
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-
?
additional information
?
-
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the enzyme catalyzes the formation of methane from methyl-coenzyme M and coenzyme B in methanogenic archaea
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-
?
additional information
?
-
-
conversion of MCRox1 toMCRred1 by Ti(III)citrate, bromopropanesulfonate is an alternative substrate of MCR in an ionic reaction that is coenzyme B-independent and leads to debromination of bromopropanesulfonate and formation of a distinct state with an EPR signal that is assigned to a Ni(III)-propylsulfonate species, propanesulfonate formation also occurs in steady-state reactions in the presence of Ti(III) citrate
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-
?
additional information
?
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the enzyme performs reactions with brominated acid, 4-bromobutyric acid to 16-bromohexadecanoic acid, analogously to the reaction of MCRred1, the active Ni(I)-F430 containing enzyme form, to generate a methyl-Ni(III) intermediate in methane formation with the natural substrate, methyl-SCoM, substrate specificity and acivities, overview
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-
?
additional information
?
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MCR catalyzes the final step in the biological synthesis of methane. Using coenzyme B, CoBSH, as the two-electron donor, MCR reduces methyl-coenzyme M, methyl-SCoM, to methane and the mixed disulfide, CoB-S-S-CoM. MCR contains coenzyme F430, an essential redox-active nickel tetrahydrocorphin, at its active site. The active form of MCR, MCRred1, contains Ni(I)-F430
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-
?
additional information
?
-
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MCR reduction/oxidation state, electron paramagnetic resonance status analysis, detailed overview
-
-
?
additional information
?
-
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MCR substrate specificity and reactivation activity of different thiols, e.g. 2-mercaptoethanol, DTT, Na2S, and cysteine, kinetics, overview
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-
?
additional information
?
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three general mechanisms for the catalytic production of methane by MCR: (1) the Ni-Me/Ragsdale pathway, (2) the Ni-Me/Thauer pathway, (3) the methyl radical pathway. Density functional calculations and electronic-structure calculations and analysis by computational methods, homolytic Ni-S/Ni-C bonds energies, overview
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-
?
additional information
?
-
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MCR is the key enzyme in methane formation by methanogenic Archaea. It converts the thioether methyl-coenzyme M and the thiol coenzyme B into methane and the heterodisulfide of coenzyme M and coenzyme B
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-
?
additional information
?
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The active form of the enzyme, referred to as MCRred1, features the tetracoordinate dx2y2 nickel(I) state of the cofactor, simulations of enzyme nickel intermediate states in synthetic complexes, mechanism and modeling, pyriporphyrin-based model and isoporphyrin-based model, overview
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?
additional information
?
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no activity with SH-CoB8 or SH-CoB9
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-
?
additional information
?
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the substrates bind inside a deep substrate channel with CoBSH nearer to the surface, stretching toward methyl-SCoM, which is close to F430
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NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
2-(methylthio)ethanesulfonate + N-(7-mercaptoheptanoyl)threonine 3-O-phosphate
CoM-S-S-CoB + methane
-
i.e. CoM and CoB
-
-
?
2-(methylthio)ethansulfonate + N-(7-mercaptoheptanoyl)threonine 3-O-phosphate
CoM-S-S-CoB + methane
-
i.e. CoM and CoB
-
-
?
methyl-coenzyme M + N-(7-mercaptoheptanoyl)threonine 3-O-phosphate (coenzyme B)
methane + CoB-S-S-CoM
-
i.e. methyl-SCoM
a the mixed disulfide
-
?
methyl-coenzyme M + N-(7-mercaptoheptanoyl)threonine 3-O-phosphate (coenzyme B)
methane + CoM-S-S-CoB
-
the enzyme catalyzes the methane forming step in methane biosynthesis by methanogenic archaea
a the mixed disulfide
-
?
CH3-S-CoM + HS-CoB
CoM-S-S-CoB + methane
-
i.e. methyl-coenzyme M + coenzyme B
-
-
?
CH3-S-CoM + HS-CoB
CoM-S-S-CoB + methane
-
key step in the convertion of C1 substrates or acetate to methane thereby providing energy for the cell
-
-
?
CH3-S-CoM + HS-CoB
CoM-S-S-CoB + methane
-
MCR catalyzes the first proposed step in anaerobic methane oxidation and terminal step in methanogenesis by using N-7-mercaptoheptanolyl-threonine phosphate, i.e. CoB-SH. as the two-electron donor to reduce 2-(methylthiol)-ethane sulfonate, i.e. methyl-SCoM, to methane, and producing the heterodisulfide, CoBS-SCoM
-
-
?
CH3-S-CoM + HS-CoB
CoM-S-S-CoB + methane
-
MCR catalyzes the methane-forming step in methanogenic archaea
-
-
?
CH3-S-CoM + HS-CoB
CoM-S-S-CoB + methane
HS-CoB is N-(7-mercaptoheptanoyl)-L-threonine 3-O-phosphate
-
-
?
CH3-S-CoM + HS-CoB
CoM-S-S-CoB + methane
-
i.e. N-7-mercaptoheptanoylthreonine phosphate, Ni(III)-methyl is an intermediate in methane formation
-
-
?
methyl-CoM + CoB
CoM-S-S-CoB + methane
-
-
-
?
additional information
?
-
-
MCR also appears to initiate anaerobic methane oxidation, the reverse methanogenesis
-
-
?
additional information
?
-
-
the enzyme catalyzes the final step in methane biosynthesis by methanogenic archaea
-
-
?
additional information
?
-
-
the enzyme catalyzes the formation of methane from methyl-coenzyme M and coenzyme B in methanogenic archaea
-
-
?
additional information
?
-
-
MCR catalyzes the final step in the biological synthesis of methane. Using coenzyme B, CoBSH, as the two-electron donor, MCR reduces methyl-coenzyme M, methyl-SCoM, to methane and the mixed disulfide, CoB-S-S-CoM. MCR contains coenzyme F430, an essential redox-active nickel tetrahydrocorphin, at its active site. The active form of MCR, MCRred1, contains Ni(I)-F430
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-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
coenzyme F430
-
2 mol of the nickel tetrapyrrole coenzyme F430, tightly bound, per enzyme hexamer, nickel is in the Ni(I) state in the active enzyme
coenzyme F430
-
a redox-active nickel tetrahydrocorphin bound at the active site, contains low-spin Ni(II), determination of the cofactor reduction site at the exocyclic ketone group by NMR study, mass spectrometry, and QM/MM computations, conversion of F430 to F330 reduces the hydrocorphin ring but not the metal, reduction of F430 with Ti(III) citrate to generate F380, corresponding to the active MCRred1 state, reduces the Ni(II) to Ni(I) but does not reduce the tetrapyrrole ring system, overview
coenzyme F430
-
an essential redox-active nickel tetrahydrocorphin, bound at the active site, the active form of MCR, MCRred1, contains Ni(I)-F430
coenzyme F430
-
each active site has the nickel porphyrinoid F430 as a prosthetic group, in the active state, F430 contains the transition metal in the Ni(I) oxidation state
coenzyme F430
-
the nickel-containing tetrapyrrole is essential for the reaction, and is bound to the active site
F-430
-
cofactor F430 undergoes a significant conformational change when it binds to the enzyme. Conversion from MCRox1 to MCRred1 involves major conformational rearrangements, which are propose to be due to a 2-electron reversible reduction of the hydrocorphin ring of F430
F-430
-
nickel-containing porphinoid cofactor F-430. Comparison of the free cofactor in the (+)1, (+)2 and (+)3 oxidation states with the cofactor bound to methyl-coenzyme M reductase in the silent, red and ox forms
F-430
-
prosthetic group has to be in the Ni(I) oxidation state for the enzyme to be active
F-430
-
tightly bound nickel porphinol. The enzyme is active only when its prosthetic group in in the NI(I)-reduced state
F-430
-
active in Ni(I) oxidation state, inactive in Ni(II) state, binding structure and oxidation states, hyperfine interactions of protons, detailed overview
F-430
-
binding structure, and different oxidation states F430 (Ni(I)/Ni(II)/Ni(III)), Ni(I) is the active state, overview
F-430
-
the active site of MCR includes a noncovalently bound Ni tetrapyrrolic coenzyme F430, which is in the Ni(I) state in the active enzyme, MCRred1
F-430
-
the enzyme has two structurally interlinked active sites embedded in an alpha2beta2gamma2 subunit structure. Each active site has the nickel porphyrinoid F430 as a prosthetic group. In the active state, F430 contains the transition metal in the Ni(I) oxidation state
F-430
-
with Ni(I) oxidation state, selectivity of the MCR reaction toward nucleophilic attack by Ni(I)
F-430
-
a nickel hydrocorphin coenzyme F430, the Ni(I) MCRred1 form and the inactive Ni(II) MCRox1-silent form, no formation of an MCRis dependent methyl-Ni(F430) species, analysis of the catalytic mechanism of the reduction at the nickel center using inhibitory fluorescent trifluoromethyl thio esters of the substrate CoB for spectroscopic analysis of the structure of the enzyme-cofactor complex, derivatives synthesis, overview
F-430
-
the Ni-F430 cofactor is bound to the active site and exists in two oxidation states
F-430
-
the active site of the enzyme contains an essential redox-active nickel tetrapyrrole cofactor, coenzyme F430, which is active in the Ni(I) state
F-430
the enzyme contains the highly reduced nickel-tetrapyrrole coenzyme F430
F-430
coenzyme F430, rapid kinetic studies rule out methyl-Ni(III) and trap the MCRox1-silent intermediate. Identification of an MCRox1-like state, specifically a F430-Ni(III)-SCoM/CoBS- intermediate, from direct DFT calculations
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Ni
Ni2+
Nickel
Ni
-
contains the nickel-containing porphinoid cofactor F-430
Ni
-
enzyme contains the tightly-bound nickel porphinol F-430 as prosthetic group
Ni
-
the active purified enzyme exhibits the axial EPR signal MCR-red1 and in the presence of coenzyme M and coenzyme B the rhombic signal MCR-red2, both derived from Ni(I). Two other EPR-detectable states of the enzyme, observed in vivo and in vitro designated MCR-ox1 and MCR-ox2 have quite different nickel EPR signals and are inactive. In vitro the MCR-red2 state is converted into the MCR-ox1 state by the addition of polysulfide and into a light-sensitive MCR-ox2 state by the addition of sulfite. In the presence of O2 the MCR-red2 state is converted into a novel third state designated MCR-ox3 and exhibits two EPR signals similar but not identical to MCR-ox1 and MCR-ox2
Ni
-
the niuckel porphinoid F-430 must be in the Ni(I) oxidation state for the enzyme to be active. The active enzyme exhibits an axial Ni(I)-based electron paramagnetic resonance signal and a UV-vis spectrum with an absorption maximum at 385 nM. This state is called the MCR-red1 state. When the temperature is lowered below 20°C the perecentage of MCR in the red2 state decreases and that in the red1 state increases. These changes with temperature are fully reversible. At most 50% of the enzyme is converted to the MCR-red2 state under all experimental conditions
Ni2+
-
each active site has the nickel porphyrinoid F430 as a prosthetic group, in the active state, F430 contains the transition metal in the Ni(I) oxidation state
Ni2+
-
in the coenzyme F430, a redox-active nickel tetrahydrocorphin bound at the active site
Ni2+
-
in the Ni-F430 cofactor, which is bound to the active site and exists in two oxidation states
Ni2+
-
nickel center in the ox1 form of methylcoenzyme M reductase, MCRox1
Ni2+
-
the enzyme contains nickel, Ni(III)-methyl is an intermediate in methane formation
Ni2+
contained in the coenzyme F430
Nickel
-
the active site of the enzyme contains an essential redox-active nickel tetrapyrrole cofactor, coenzyme F430, which is active in the Ni(I) state
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(+)-(2S,3R)-N-[7-(methylthio)heptanoyl]-O-phospho-L-threonine
-
CoB substrate thioester derivative, synthesis, spectral analysis and binding structure, overview
(+)-(2S,3R)-N-[7-(trifluoromethylthio)heptanoyl]-O-phospho-L-threonine
-
fluorescent CoB substrate thioester derivative, synthesis, spectral analysis and binding structure, overview
3-bromopropanesulfonate
-
irreversible, strong inhibitor and competitive substrate
4-bromobutane sulfonate
-
when reacted with 4-bromobutyrate, MCRred1 forms the alkyl-Ni(III) MCRXA state and then self-reactivation to regenerate the Ni(I) MCRred1 state and a bromocarboxy ester
bromopropanesulfonate
-
BPS, a potent inhibitor and reversible redox inactivator that reacts with MCRred1 to form an EPR-active state called MCRPS, which is an alkyl-nickel species. Treatment of MCRPS with free thiol containing compounds leads to reconvertion to the active MCRred1 state
HS-CoM
-
the unmethylated coenzyme M is a reversible competitive inhibitor
O-phosphono-N-(5-sulfanylpentanoyl)-L-threonine
-
O-phosphono-N-(6-sulfanylhexanoyl)-L-threonine
-
3-bromopropane sulfonate
-
BPS, forms an alkyl-Ni(III) species with MCRred1is that elicits the MCRPS EPR signal; irreversible inhibition
additional information
-
inhibition mechanism, brominated carboxylic acids, with carbon chain lengths of 4-16, all give rise to an alkyl-Ni intermediate with an EPR signal similar to that of the MCRPS species, brominated carboxylic acids mimic the interactions of BPS and methyl-SCoM at the MCR active site, overview
-
additional information
-
pharmacokinetics of 35 compounds from rhubarb (Rheum sp.), molecular docking simulation and ADME analysis. Rhubarb has anti-methanogenic activity, usage of in silico analysis on methyl-coenzyme M reductase (MCR) for identifying its anti-methanogen mechanism. Three possible candidate show minimum binding energy (kcal/mol) with the target protein MCR which catalyze the biosynthesis of rumen methane. The decrease in ruminal methane emission by rhubarb might be a result of these compounds by inhibition of methanogenesis
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.03
CH3-S-CoM
-
with SH-CoB6 as cosubstrate, pH not specified in the publication, at 25°C
0.28
CH3-S-CoM
-
with SH-CoB5 as cosubstrate, pH not specified in the publication, at 25°C
additional information
additional information
-
steady-state and rapid kinetics, MCRred1-catalyzed cleavage of the C-S bond of methyl-SCoM requires the other substrate, HSCoB, even under single turnover conditions
-
additional information
additional information
-
steady-state kinetics of MCRred1 with brominated acids, overview
-
additional information
additional information
-
stopped flow kinetics, overview
-
additional information
additional information
-
transient kinetics study, overview
-
additional information
additional information
transient kinetic, spectroscopic [ultraviolet-visible (UV-Vis), EPR, and MCD], and computational studies of the first step in the MCR catalytic mechanism are performed to trap and identify the key intermediates that differ between proposed mechanisms I and II, detailed overview. Rapid kinetic studies rule out methyl-Ni(III) and trap the MCRox1-silent intermediate
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0001
O-phosphono-N-(6-sulfanylhexanoyl)-L-threonine
pH and temperature not specified in the publication
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7.6
additional information
-
pH 10.0 is optimal for activation of MCRox1 to MCRred1 with Ti(III) citrate
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
661554, 661921, 661943, 662465, 662466, 662467, 662468, 662469, 672069, 672222, 690930, 693838, 702287, 703210, 724279, 725201, 737451, 762394
-
-
formerly Methanobacterium thermoautotrophicum, strain Marburg
-
-
formerly Methanothermobacter thermoautotrophicum strain Marburg
-
-
i.e. Methanothermobacter thermoautotrophicum strain Marburg
-
-
i.e. Methanothermobacter thermoautotrophicum strain Marburg, DSM 2133
-
-
or Methanothermobacter thermoautotrophicum strain Marburg, DSM 2133
-
-
subunits A, B, and G encoded by genes mcrA, mcrB, and mcrG
UniProt
subunits alpha, beta and gamma
UniProt
subunits alpha, beta, and gamma; Methanobacterium thermoautotrophicum
UniProt
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
facultative membrane association under growth limiting conditions on nickel-depleted media
-
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
metabolism
physiological function
the enzyme that catalyzes the chemical step of methane synthesis or oxidation is methyl-coenzyme M reductase (MCR), which contains a nickel hydrocorphinate F430 at its active site. This reaction involves conversion of the methyl donor, methylcoenzyme M (methyl-SCoM), and the electron donor, coenzyme B (CoBSH, N-7-mercaptoheptanoylthreonine phosphate), to methane and the mixed disulfide CoBS-SCoM
additional information
initial steps in three proposed mechanisms of MCR catalysis: (i) mechanism I involves nucleophilic attack of Ni(I)-MCRred1 on the methyl group of methyl-SCoM to generate a methyl-Ni(III) intermediate. This mechanism is similar to that of B12-dependent methyltransferases, which generate a methyl-cob(III) alamin intermediate. (ii) In mechanism II, Ni(I) attack on the sulfur atom of methyl-SCoM promotes the homolytic cleavage of the methyl-sulfur bond to produce a methyl radical and a Ni(II)-thiolate. (iii) Mechanism III involves nucleophilic attack of Ni(I) on the sulfur of methyl-SCoM to form a highly reactive methyl anion and Ni(III)-SCoM (MCRox1)
metabolism
-
MCR catalyzes the terminal step in the formation of biological methane from methyl-coenzyme M and coenzyme B
metabolism
-
the enzyme catalyzes the final step in methanogenesis
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). PDB
SCOP
CATH
UNIPROT
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
heterotrimer
hexamer
trimer
methyl coenzyme M reductase (MCR) is composed of three subunits, alpha2, beta2, and gamma2
additional information
additional information
-
enzyme structure analysis in reduced and oxidized state, the enzyme has two structurally interlinked active sites embedded in an a2b2c2 subunit structure, overview
additional information
-
the enzyme has two structurally interlinked active sites embedded in an alpha2beta2gamma2 subunit structure. Each active site has the nickel porphyrinoid F430 as a prosthetic group
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
side-chain modification
-
methylation of residues in the active site, e.g. at His257, 5fold methylation in isozyme MCR I, overview
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
enzyme alone and in complex with substrates, sitting drop vapor diffusion method, using 100 mM Na-HEPES, pH 7.3-8.0, 150 mM magnesium acetate, and 20-22% (w/v) PEG 400
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
identifying the key intermediate in methanogenesis provides fundamental insights to develop better catalysts for producing and activating an important fuel and potent greenhouse gas
additional information
methyl-coenzyme M reductase-dependent methane production enhances plant tolerance against abiotic stress and alters abscisic acid (ABA) sensitivity in Arabidopsis thaliana expressing enzyme MtMCR from Methanobacterium thermoautotrophicum, phenotype, overview. MCR-dependent endogenous CH4 enhances abiotic tolerance during seed germination and post-germination stages. MCR-dependent CH4-triggers the salinity and osmotic stress tolerance via the reestablishment of redox homeostasis
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
native enzyme, during purification the enzyme lost its MCR-red2 signal owing to the removal of HS-CoB
-
purification of native MCRox1, and of native MCRred1, the latter by ammonium sulfate fractionation and ion exchange chromatography
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant enzyme constitutive expression in Arabidopsis thaliana under the control of CaMV35S promoter via an Agrobacterium-mediated floral-dip transformation, semi-quantitative RT-PCR and quantitative real-time PCR enzyme expression analysis
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Ermler, U.
On the mechanism of methyl-coenzyme M reductase
Dalton Trans.
2005
3451-3458
2005
Methanothermobacter marburgensis
Tang, Q.; Carrington, P.E.; Horng, Y.C.; Maroney, M.J.; Ragsdale, S.W.; Bocian, D.F.
X-ray absorption and resonance Raman studies of methyl-coenzyme M reductase indicating that ligand exchange and macrocycle reduction accompany reductive activation
J. Am. Chem. Soc.
124
13242-13256
2002
Methanothermobacter marburgensis
Harmer, J.; Finazzo, C.; Piskorski, R.; Bauer, C.; Jaun, B.; Duin, E.C.; Goenrich, M.; Thauer, R.K.; Van Doorslaer, S.; Schweiger, A.
Spin density and coenzyme M coordination geometry of the ox1 form of methyl-coenzyme M reductase: A Pulse EPR Study
J. Am. Chem. Soc.
127
17744-17755
2005
Methanothermobacter marburgensis
Goenrich, M.; Duin, E.C.; Mahlert, F.; Thauer, R.K.
Temperature dependence of methyl-coenzyme M reductase activity and of the formation of the methyl-coenzyme M reductase red2 state induced by coenzyme B
J. Biol. Inorg. Chem.
10
333-342
2005
Methanothermobacter marburgensis
Mahlert, F.; Grabarse, W.; Kahnt, J.; Thauer, R.K.; Duin, E.C.
The nickel enzyme methyl-coenzyme M reductase from methanogenic archaea: in vitro interconversions among the EPR detectable MCR-red1 and MCR-red2 states
J. Biol. Inorg. Chem.
7
101-112
2002
Methanothermobacter marburgensis
Mahlert, F.; Bauer, C.; Jaun, B.; Thauer, R.K.; Duin, E.C.
The nickel enzyme methyl-coenzyme M reductase from methanogenic archaea: In vitro induction of the nickel-based MCR-ox EPR signals from MCR-red2
J. Biol. Inorg. Chem.
7
500-513
2002
Methanothermobacter marburgensis
Duin, E.C.; Signor, L.; Piskorski, R.; Mahlert, F.; Clay, M.D.; Goenrich, M.; Thauer, R.K.; Jaun, B.; Johnson, M.K.
Spectroscopic investigation of the nickel-containing porphinoid cofactor F(430). Comparison of the free cofactor in the (+)1, (+)2 and (+)3 oxidation states with the cofactor bound to methyl-coenzyme M reductase in the silent, red and ox forms
J. Biol. Inorg. Chem.
9
563-576
2004
Methanothermobacter marburgensis
Goenrich, M.; Mahlert, F.; Duin, E.C.; Bauer, C.; Jaun, B.; Thauer, R.K.
Probing the reactivity of Ni in the active site of methyl-coenzyme M reductase with substrate analogues
J. Biol. Inorg. Chem.
9
691-705
2004
Methanothermobacter marburgensis
Dey, M.; Kunz, R.C.; Van Heuvelen, K.M.; Craft, J.L.; Horng, Y.C.; Tang, Q.; Bocian, D.F.; George, S.J.; Brunold, T.C.; Ragsdale, S.W.
Spectroscopic and computational studies of reduction of the metal versus the tetrapyrrole ring of coenzyme F430 from methyl-coenzyme M reductase
Biochemistry
45
11915-11933
2006
Methanothermobacter marburgensis
Dey, M.; Kunz, R.C.; Lyons, D.M.; Ragsdale, S.W.
Characterization of alkyl-nickel adducts generated by reaction of methyl-coenzyme M reductase with brominated acids
Biochemistry
46
11969-11978
2007
Methanothermobacter marburgensis
Kahnt, J.; Buchenau, B.; Mahlert, F.; Krueger, M.; Shima, S.; Thauer, R.K.
Post-translational modifications in the active site region of methyl-coenzyme M reductase from methanogenic and methanotrophic archaea
FEBS J.
274
4913-4921
2007
Methanocaldococcus jannaschii, Methanococcus voltae, Methanoculleus thermophilus, Methanopyrus kandleri, Methanopyrus kandleri (Q49605), Methanosarcina barkeri, Methanothermobacter marburgensis
Kunz, R.C.; Horng, Y.C.; Ragsdale, S.W.
Spectroscopic and kinetic studies of the reaction of bromopropanesulfonate with methyl-coenzyme M reductase
J. Biol. Chem.
281
34663-34676
2006
Methanothermobacter marburgensis
Kern, D.I.; Goenrich, M.; Jaun, B.; Thauer, R.K.; Harmer, J.; Hinderberger, D.
Two sub-states of the red2 state of methyl-coenzyme M reductase revealed by high-field EPR spectroscopy
J. Biol. Inorg. Chem.
12
1097-1105
2007
Methanothermobacter marburgensis
Kunz, R.C.; Dey, M.; Ragsdale, S.W.
Characterization of the thioether product formed from the thiolytic cleavage of the alkyl-nickel bond in methyl-coenzyme M reductase
Biochemistry
47
2661-2667
2008
Methanothermobacter marburgensis
Harmer, J.; Finazzo, C.; Piskorski, R.; Ebner, S.; Duin, E.C.; Goenrich, M.; Thauer, R.K.; Reiher, M.; Schweiger, A.; Hinderberger, D.; Jaun, B.
A nickel hydride complex in the active site of methyl-coenzyme M reductase: implications for the catalytic cycle
J. Am. Chem. Soc.
130
10907-10920
2008
Methanothermobacter marburgensis
Hinderberger, D.; Ebner, S.; Mayr, S.; Jaun, B.; Reiher, M.; Goenrich, M.; Thauer, R.K.; Harmer, J.
Coordination and binding geometry of methyl-coenzyme M in the red1m state of methyl-coenzyme M reductase
J. Biol. Inorg. Chem.
13
1275-1289
2008
Methanothermobacter marburgensis
Duin, E.C.; McKee, M.L.
A new mechanism for methane production from methyl-coenzyme M reductase as derived from density functional calculations
J. Phys. Chem. B
112
2466-2482
2008
Methanothermobacter marburgensis
Sarangi, R.; Dey, M.; Ragsdale, S.W.
Geometric and electronic structures of the Ni(I) and methyl-Ni(III) intermediates of methyl-coenzyme M reductase
Biochemistry
48
3146-3156
2009
Methanothermobacter marburgensis
Gonzalez, E.; Ghosh, A.
Models of the ox1 state of methylcoenzyme M reductase: where are the electrons?
Chemistry
14
9981-9989
2008
Methanothermobacter marburgensis
Ebner, S.; Jaun, B.; Goenrich, M.; Thauer, R.K.; Harmer, J.
Binding of coenzyme B induces a major conformational change in the active site of methyl-coenzyme M reductase
J. Am. Chem. Soc.
132
567-575
2010
Methanothermobacter marburgensis
Wrede, C.; Walbaum, U.; Ducki, A.; Heieren, I.; Hoppert, M.
Localization of methyl-coenzyme M reductase as metabolic marker for diverse methanogenic Archaea
Archaea
2013
920241
2013
Methanococcus maripaludis, Methanococcus maripaludis DSM 2067, Methanosarcina mazei, Methanosarcina mazei DSM 3318, Methanosarcina mazei DSM 3647, Methanothermobacter marburgensis, Methanothermobacter marburgensis DSM 2133, Methanothermobacter wolfeii, Methanothermobacter wolfeii DSM 2970
Dey, M.; Li, X.; Kunz, R.C.; Ragsdale, S.W.
Detection of organometallic and radical intermediates in the catalytic mechanism of methyl-coenzyme M reductase using the natural substrate methyl-coenzyme M and a coenzyme B substrate analogue
Biochemistry
49
10902-10911
2010
Methanothermobacter marburgensis, Methanothermobacter marburgensis OCM82
Cedervall, P.E.; Dey, M.; Pearson, A.R.; Ragsdale, S.W.; Wilmot, C.M.
Structural insight into methyl-coenzyme M reductase chemistry using coenzyme B analogues
Biochemistry
49
7683-7693
2010
Methanothermobacter marburgensis (P11558 and P11560 and P11562), Methanothermobacter marburgensis OCM82 (P11558 and P11560 and P11562)
Cedervall, P.E.; Dey, M.; Li, X.; Sarangi, R.; Hedman, B.; Ragsdale, S.W.; Wilmot, C.M.
Structural analysis of a Ni-methyl species in methyl-coenzyme M reductase from Methanothermobacter marburgensis
J. Am. Chem. Soc.
133
5626-5628
2011
Methanothermobacter marburgensis
Wagner, T.; Kahnt, J.; Ermler, U.; Shima, S.
Didehydroaspartate modification in methyl-coenzyme M reductase catalyzing methane formation
Angew. Chem. Int. Ed. Engl.
55
10630-10633
2016
Methanosarcina barkeri, Methanothermobacter wolfeii, Methanothermobacter marburgensis
Wongnate, T.; Ragsdale, S.W.
The reaction mechanism of methyl-coenzyme M reductase: how an enzyme enforces strict binding order
J. Biol. Chem.
290
9322-9334
2015
Methanothermobacter marburgensis
Su, J.; Yang, X.; He, J.; Zhang, Y.; Duan, X.; Wang, R.; Shen, W.
Methyl-coenzyme M reductase-dependent endogenous methane enhances plant tolerance against abiotic stress and alters ABA sensitivity in Arabidopsis thaliana
Plant Mol. Biol.
101
439-454
2019
Methanothermobacter marburgensis (P11558 and P11560 and P11562), Methanothermobacter marburgensis Marburg (P11558 and P11560 and P11562), Methanothermobacter marburgensis ATCC BAA-927 (P11558 and P11560 and P11562), Methanothermobacter marburgensis NBRC 100331 (P11558 and P11560 and P11562), Methanothermobacter marburgensis JCM 14651 (P11558 and P11560 and P11562), Methanothermobacter marburgensis DSM 2133 (P11558 and P11560 and P11562), Methanothermobacter marburgensis OCM 82 (P11558 and P11560 and P11562)
Arokiyaraj, S.; Stalin, A.; Shin, H.
Anti-methanogenic effect of rhubarb (Rheum spp.) - an in silico docking studies on methyl-coenzyme M reductase (MCR)
Saudi J. Biol. Sci.
26
1458-1462
2019
Methanothermobacter marburgensis
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