Tetrahydromethanopterin

THMPT is the main platform for C1 transformations

N-Formylmethanofuran donates the C1 group to the N5 site of the pterin to give the formyl- THMPT. The formyl group subsequently condenses intramolecularly to give methenyl-, which is then reduced to methylene-THMPT by 5,10-methenyl- hydrogenase with as the electron donor. Methylene- MPT is subsequently converted, using coenzyme F420 as the electron source, to methyl-THMPT, catalyzed by F420-dependent methylene-THMPT reductase. Methyl-THMPT is the methyl donor to coenzyme M, a conversion mediated by methyl-THMPT: coenzyme M methyltransferase.

Comparison with tetrahydrofolic acid

THMPT is related to the better known tetrahydrofolic acid (THFA, ). The most important difference between THMPT and THFA is that THFA has an electron-withdrawing carbonyl group on the phenyl ring. As a consequence, methenyl- THMPT is more difficult to reduce than methenyl- THFA. Reduction is effected by a so-called iron-sulfur cluster free hydrogenase. The cumbersome name distinguishes this hydrogenase from the so-called Fe-only hydrogenases that do contain Fe-S cluster.

References

References

1. Thauer RK. (September 1998). "Biochemistry of methanogenesis: a tribute to Marjory Stephenson. 1998 Marjory Stephenson Prize Lecture". Microbiology.
2. (March 2006). "The structure of formylmethanofuran: tetrahydromethanopterin formyltransferase in complex with its coenzymes". J. Mol. Biol..
3. (October 2006). "The iron-sulfur cluster-free hydrogenase (Hmd) is a metalloenzyme with a novel iron binding motif". J. Biol. Chem..