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Catalytic Site Atlas Version 2.2.12
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CSA entry for 1mro
Original Entry
Title:
Methanogenesis
Compound:
Methyl-coenzyme m reductase
Mutant:
No
UniProt/Swiss-Prot:
O27232-MCRA_METTH
O27233-MCRG_METTH
O27236-MCRB_METTH
EC Class:
2.8.4.1
Other CSA Entries:
Overview of all sites for 1mro
Homologues of 1mro
Entries for UniProt/Swiss-Prot: O27232
Entries for UniProt/Swiss-Prot: O27233
Entries for UniProt/Swiss-Prot: O27236
Entries for EC: 2.8.4.1
Other Databases:
PDB entry: 1mro
PDBsum entry: 1mro
UniProt/Swiss-Prot: O27232
UniProt/Swiss-Prot: O27233
UniProt/Swiss-Prot: O27236
IntEnz entry: 2.8.4.1
Literature Report:
Introduction:
Methyl coenzyme M Reductase is responsible for the last step in methane production by methanogenic archaea. It utilises the ability of Nickel to adopt oxidation states I, II and III in order to catalyse the conversion of methyl coenzyme M and methyl coenzyme B to give methane and a heterodisulphide compound between the two coenzymes, in a complex redox cycle. The enzyme, like many found in archaea, is able to withstand high temperatures and salt content.
Mechanism:
The reaction proceeds in a cycle. Starting with the activation of coenzyme B by Asn 501, a thiolpeptide bond between Gly A465 and Tyr A466 accepts a single electron from the sulphur atom of coenzyme B to form a thioketyl radical that reduces Ni(III) bound to a methyl group to Ni (II). Protonation by Tyrosine B367 then occurs resulting in methane release. Meanwhile the coenzyme B radical reacts with methyl coenzyme M forming a methylcoM-coB disulphide radical. This in turn loses its methyl group to Ni (I), the oxidation state of the enzyme when no substrate is bound, forming methyl bound Ni (II) and generating a disulphide anion radical which reduces the Ni (II) previously generated to Ni (I) so that it can accept the methyl group and continue the cycle.
Sites:

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Found by:
Literature reference 

ResidueChainNumberUniProt numberFunctional part FunctionTargetDescription
700 0
ElectrostaticSubstrate
Ni (I) is able to accept the methyl group from methyl coenzyme M, thus forming Ni (III) and allowing eventual release of methane through regeneration of Ni (I).
Evidence from paper Evidence concerns Evidence type
PubMed ID 11491299 Current protein Ligand is essential for catalysis

ResidueChainNumberUniProt numberFunctional part FunctionTargetDescription
GLYA 465 0Sidechain
Radical formationSubstrate
The peptide bond between Gly 465 and Tyr 466 is modified to contain a sulphur atom in place of a nitrogen; thus it can accept an electron from coenzyme M to form a thioketyl radical which then in turn passes the electron to Ni(III), reducing it.
Evidence from paper Evidence concerns Evidence type
PubMed ID 11023796 Current protein Conservation of residue
PubMed ID 11023796 Current protein Residue is positioned appropriately (ligand position known)

ResidueChainNumberUniProt numberFunctional part FunctionTargetDescription
ASPA 501 0Sidechain
Acid/baseSubstrate
Acts to activate coenzyme B by deprotonation so that it can donate an electron to the thiopeptide bond and subsequently react with methylcoenzyme M.
Evidence from paper Evidence concerns Evidence type
PubMed ID 11491299 Current protein Residue is positioned appropriately (ligand position known)

ResidueChainNumberUniProt numberFunctional part FunctionTargetDescription
TYRB 367 0Sidechain
Acid/baseSubstrate
Protonates methyl group attached to Nickel cofactor resulting in the release of methane and the regeneration of Ni(I) to complete the redox cycle.
Evidence from paper Evidence concerns Evidence type
PubMed ID 11491299 Current protein Residue is positioned appropriately (ligand position known)
PubMed ID 11491299 Current protein Conservation of residue
References:
1
Comparison of three methyl-coenzyme M reductases from phylogenetically distant organisms: unusual amino acid modification, conservation and adaptation.
W. Grabarse and F. Mahlert and S. Shima and R. K. Thauer and U. Ermler
J Mol Biol 303, (2) 329-44, (2000).
11023796
2
On the mechanism of biological methane formation: structural evidence for conformational changes in methyl-coenzyme M reductase upon substrate binding.
W. Grabarse and F. Mahlert and E. C. Duin and M. Goubeaud and S. Shima and R. K. Thauer and V. Lamzin and U. Ermler
J Mol Biol 309, (1) 315-30, (2001).
11491299
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