2FHJ

Crystal structure of formylmethanofuran: tetrahydromethanopterin formyltransferase in complex with its coenzymes

Summary for 2FHJ

• Entry DOI: 10.2210/pdb2fhj/pdb
• Related: 1FTR 1M5H 1M5S 2FHK
• Descriptor: Formylmethanofuran--tetrahydromethanopterin formyltransferase, POTASSIUM ION, N-[4,5,7-TRICARBOXYHEPTANOYL]-L-GAMMA-GLUTAMYL-N-{2-[4-({5-[(FORMYLAMINO)METHYL]-3-FURYL}METHOXY)PHENYL]ETHYL}-D-GLUTAMINE, ... (8 entities in total)
• Functional Keywords: tetrahydromethanopterin; methanofuran; c1 metabolism; formyltransferase; complex, transferase
• Biological source: Methanopyrus kandleri; More
• Cellular location: Cytoplasm: Q49610 Q49610
• Total number of polymer chains: 4
• Total formula weight: 133840.87

Authors

Acharya, P.,Warkentin, E.,Thauer, R.K.,Shima, S.,Ermler, U. (deposition date: 2005-12-25, release date: 2006-03-07, Last modification date: 2024-11-06)

Primary citation

Acharya, P.,Warkentin, E.,Ermler, U.,Thauer, R.K.,Shima, S.
The structure of formylmethanofuran: tetrahydromethanopterin formyltransferase in complex with its coenzymes
J.Mol.Biol., 357:870-879, 2006

PubMed Abstract: Formylmethanofuran:tetrahydromethanopterin formyltransferase is an essential enzyme in the one-carbon metabolism of methanogenic and sulfate-reducing archaea and of methylotrophic bacteria. The enzyme, which is devoid of a prosthetic group, catalyzes the reversible formyl transfer between the two substrates coenzyme methanofuran and coenzyme tetrahydromethanopterin (H4MPT) in a ternary complex catalytic mechanism. The structure of the formyltransferase without its coenzymes has been determined earlier. We report here the structure of the enzyme in complex with both coenzymes at a resolution of 2.0 A. Methanofuran, characterized for the first time in an enzyme structure, is embedded in an elongated cleft at the homodimer interface and fixed by multiple hydrophobic interactions. In contrast, tetrahydromethanopterin is only weakly bound in a shallow and wide cleft that provides two binding sites. It is assumed that the binding of the bulky coenzymes induces conformational changes of the polypeptide in the range of 3A that close the H4MPT binding cleft and position the reactive groups of both substrates optimally for the reaction. The key residue for substrate binding and catalysis is the strictly conserved Glu245. Glu245, embedded in a hydrophobic region and completely buried upon tetrahydromethanopterin binding, is presumably protonated prior to the reaction and is thus able to stabilize the tetrahedral oxyanion intermediate generated by the nucleophilic attack of the N5 atom of tetrahydromethanopterin onto the formyl carbon atom of formylmethanofuran.

PubMed: 16466742
DOI: 10.1016/j.jmb.2006.01.015

Experimental method

X-RAY DIFFRACTION (2 Å)