4AY8

SeMet-derivative of a methyltransferase from M. mazei

Summary for 4AY8

• Entry DOI: 10.2210/pdb4ay8/pdb
• Related: 4AY7
• Descriptor: METHYLCOBALAMIN\: COENZYME M METHYLTRANSFERASE, 1-THIOETHANESULFONIC ACID, ZINC ION, ... (6 entities in total)
• Functional Keywords: transferase
• Biological source: METHANOSARCINA MAZEI
• Total number of polymer chains: 2
• Total formula weight: 76197.11

Authors

Hoeppner, A.,Thomas, F.,Rueppel, A.,Hensel, R.,Blankenfeldt, W.,Bayer, P.,Faust, A. (deposition date: 2012-06-18, release date: 2012-10-31, Last modification date: 2024-10-23)

Primary citation

Hoeppner, A.,Thomas, F.,Rueppel, A.,Hensel, R.,Blankenfeldt, W.,Bayer, P.,Faust, A.
Structure of the Corrinoid:Coenzyme M Methyltransferase Mtaa from Methanosarcina Mazei
Acta Crystallogr.,Sect.D, 68:1549-, 2012

PubMed Abstract: The zinc-containing corrinoid:coenzyme M methyltransferase MtaA is part of the methanol-coenzyme M-methyltransferase complex of Methanosarcina mazei. The whole complex consists of three subunits: MtaA, MtaB and MtaC. The MtaB-MtaC complex catalyses the cleavage of methanol (bound to MtaB) and the transfer of the methyl group onto the cobalt of cob(I)alamin (bound to MtaC). The MtaA-MtaC complex catalyses methyl transfer from methyl-cob(III)alamin (bound to MtaC) to coenzyme M (bound to MtaA). The crystal structure of the MtaB-MtaC complex from M. barkeri has previously been determined. Here, the crystal structures of MtaA from M. mazei in a substrate-free but Zn(2+)-bound state and in complex with Zn(2+) and coenzyme M (HS-CoM) are reported at resolutions of 1.8 and 2.1 Å, respectively. A search for homologous proteins revealed that MtaA exhibits 23% sequence identity to human uroporphyrinogen III decarboxylase, which has also the highest structural similarity (r.m.s.d. of 2.03 Å for 306 aligned amino acids). The main structural feature of MtaA is a TIM-barrel-like fold, which is also found in all other zinc enzymes that catalyse thiol-group alkylation. The active site of MtaA is situated at the narrow bottom of a funnel such that the thiolate group of HS-CoM points towards the Zn(2+) ion. The Zn(2+) ion in the active site of MtaA is coordinated tetrahedrally via His240, Cys242 and Cys319. In the substrate-free form the fourth ligand is Glu263. Binding of HS-CoM leads to exchange of the O-ligand of Glu263 for the S-ligand of HS-CoM with inversion of the zinc geometry. The interface between MtaA and MtaC for transfer of the methyl group from MtaC-bound methylcobalamin is most likely to be formed by the core complex of MtaB-MtaC and the N-terminal segment (a long loop containing three α-helices and a β-hairpin) of MtaA, which is not part of the TIM-barrel core structure of MtaA.

PubMed: 23090404
DOI: 10.1107/S090744491203853X

Experimental method

X-RAY DIFFRACTION (2.1 Å)