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Cofactor F430 is porphinoid with a nickel center. Due to the incorporation of a mixture of fundamental components of porphyrins and corrins it can be appropriately classified as a
"tetrahydroderivative of the corphin system"
. [1]
Proposed Mechanisms
[edit]Two highly debatable mechanisms for the catalytic activity of F430 in methane production have been resolved. The active enzyme contains the free cofactor F430 with nickel in the Ni (I) oxidation state. Both mechanisms require the binding of methyl-coenzyme M, which stimulates a structural modification of the active site and coenzyme B subsequently binds. The catalytic synthesis of methane occurs within a hydrophobic compartment due to the blocking of the substrate channel opening by the bulky mercaptoheptanoyl group of coenzyme B.[2]
Mechanism 1
[edit]Ni(I)F430 initiates the heterolytic cleavage of the methyl-coenzyme M thioether bond, and the nucleophilic attachment of the resulting methyl cation to the cofactor oxidizes the nickel from Ni(I) to Ni(III) in a methyl-Ni(III)F430 complex.[2] The other product of the cleavage, a coenzyme M thiolate, is protonated by coenzyme B in a complimentary reaction.[3]
CoB-S-H + CH3-S-CoM + Ni(I)F430 → CoB-S- + H-S-CoM + CH3-Ni(III)F430+[3]
Ni(III) induces the oxidation of coenzyme M thiolate, in which the methyl-Ni(III) complex gains an electron, reducing Ni(III) to Ni(II) and yielding the thiyl radical of coenzyme M.[2]
H-S-CoM + CH3-Ni(III)F430+ → H-*S-CoM+ + CH3-Ni(II)F430 [3]
Methane is released upon the protonation of the methyl group of the methyl- Ni(II)F430 intermediate by the alcohol side chain of TyrB367. A concurrent proton transfer from coenzyme B reprotonates TyrB367 and a disulfide bond couples the resultant coenzyme B thiolate anion and the coenzyme M thiyl.[2] The catalytic cycle is completed by the reduction of Ni(II) back to its initial Ni(I) oxidation state by abstraction of an electron from the coenzyme M-coenzyme B radical anion.[2]
H-S-CoB + H-*S-CoM+ + CH3-Ni(II)F430 → CH4 + CoB-S-S-CoM + Ni(I)F430 [3]
Mechanism 2
[edit]The second mechanism similarly consists of the Ni(I)F430 induced nucleophilic substitution of the methyl-coenzyme M thioether bond, however, the bond is broken homolytically rather than hetereolytically. The homolytic cleavage releases a methyl radical and a coenzyme M radical , the latter of which combines with Ni(I)F430, oxidizing Ni(I) to Ni(II).[2]
CoB-S-H + CH3-S-CoM + Ni(I)F430 → CoB-S-H + *CH3 + CoM-S-Ni(II)F430 [3]
Proton transfer from coenzyme B to the methyl radical expels methane and a coenzyme B thiyl radical, which is involved in a substitution reaction with the coenzyme M-Ni(II)F430 complex to yield the heterodisulfide radical anion. The reduction of the nickel of the cofactor to its original Ni(I) oxidation state is complimented by the oxidation of the coenzyme M-coenzyme B radical anion, terminating the catalytic cycle.[2]
CoB-S-H + *CH3+ → CoB-S* + CH4 [3]
CoB-S* + CoM-S-Ni(II)F430 → CoB-S-S-CoM + Ni(I)F430 [3]
References
[edit]- ^ Gilles, Harald; Thauer, Rudolf K. (1983). "Uroporphyrinogen 111, an intermediate in the biosynthesis of the nickel-containing factor F430 in Methanobacterium thermoautotrophicum". European Journal of Biochemistry. 135 (1): 1. doi:10.1039/B506697B.
- ^ a b c d e f g Shima, Seigo; Warkentin, Eberhard; Thauer, Rudolf K.; Ermler, Ulrich (2002). "Structure and Function of Enzymes Involved in the Methanogenic Pathway Utilizing Carbon Dioxide and Molecular Hydrogen". Jounral of Bioscience and Bioengineering. 93 (6): 525–527. doi:10.1016/S1389-1723(02)80232-8.
- ^ a b c d e f g Pelmenschikov, Vladimir; Siegbahn, Per E.M. (July 2003). "Catalysis by Methyl-Coenzyme M Reductase: A Theoretical Study for Heterodisulfide Product Formation". Journal of Biological Inorganic Chemistry. 8: 654–656.