3.C.1 The Na+ Transporting Methyltetrahydromethanopterin:Coenzyme M Methyltransferase (NaT-MMM) Family

The NaT-MMM (EC 2.1.1.86) of Methanobacterium thermoautotrophicumhas been purified and characterized, and the Na+ transport reaction has been studied in inverted membrane vesicles. Sequencing of the encoding genes revealed eight contiguous genes organized in an operon. The majority of the encoded subunits are probably integral membrane proteins. Thus, MtrA, B, F and G have 1 TMS; MtrC has 7; MtrD has 6; MtrE has 6; and MtrH has none (Gottschalk and Thauer, 2001). MtrE is believed to be the Na+-transporting subunit. MtrA bears a cob(I)amide prosthetic group which is methylated and demethylated in the catalytic cycle. Demethylation is the Na+-dependent step. Thus, methyl transfer from methylated MtrA to coenzyme M drives the electrogenic translocation of Na+. The overall methyl transfer reaction is strongly exergonic (ΔG°= -30 kJ/mol) (Gottschalk and Thauer, 2001).

The NaT-MMM complex probably contains iron/sulfur clusters. As noted above, the enzyme catalyzes two chemical reactions as follows:

(1) CH3-H4MPT + E:Co(I) → H4MPT + E:CH3-Co(III).

(2) E:CH3-Co(III) + HS-CoM → E:Co(I) + CH3-S-CoM.

Reaction 1 is reversible, but reaction 2 is essentially irreversible in the direction shown. Na+ efflux is probably coupled to the second of these two reactions.

The generalized transport reaction is therefore probably:

Na+ (in) + E:CH3-Co(III) + HS-CoM  Na+ (out) + E:Co(I) + CH3-S-CoM.


 

References:

Becher, B., V. Müller and G. Gottschalk (1992a). The methyl-tetrahydromethanopterin-coenzyme-M methyltransferase of Methanosarcina strain GO1 is a primary sodium pump. FEMS Microbiol. Lett. 91: 239-244.

Becher, B., V. Müller and G. Gottschalk (1992b). N-5-methyl-tetrahydromethanopterin-coenzyme-M methyltransferase of Methanosarcina strain GO1 is an Na+-translocating membrane protein. J. Bacteriol. 174: 7656-7660

Dimroth, P. (1997). Primary sodium ion translocating enzymes. Biochim. Biophys. Acta 1318: 11-51.

Gottschalk, G. and R.K. Thauer (2001). The Na+-translocating methyltransferase complex from methanogenic archaea. Biochim. Biophys. Acta. 1505: 28-36.

Harms, U., D.S. Weiss, P. Gärtner, D. Linder, and R.K. Thauer. (1995). The energy conserving N5-methyltetrahydromethanopterin:coenzyme M methyltransferase complex from Methanobacterium thermoautotrophicum is composed of eight different subunits. Eur J Biochem 228: 640-648.

Stupperich, E., A. Juza, M. Hoppert and F. Mayer (1993). Cloning, sequencing and immunological characterization of the corrinoid-containing subunit of the N5-methyltetrahydromethanopterin:coenzyme-M methyltransferase from Methanobacterium thermoautotrophicum. Eur. J. Biochem. 217: 115-121.

Examples:

TC#NameOrganismal TypeExample
3.C.1.1.1

Na+-transporting tetrahydromethanopterin S-methyltransferase (NMM), MtrABCDEFGH (Harms et al. 1995).

Archaea

NMM of Methanothermobacter marburgensis (Methanobacterium thermoautotrophicum)
MtrA, Chain A, (238 residues); MtrB, Chain B, (100 residues); MtrC, Chain C, (267 residues); MtrD, Chain D, (233 residues); MtrE, Chain 1, (295 residues); MtrF, Chain 2, (68 residues); MtrG, Chain 3, (86 residues); MtrH, Chain 4, (310 residues)