2fhk
From Proteopedia
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Crystal structure of formylmethanofuran: tetrahydromethanopterin formyltransferase in complex with its coenzymes
Overview
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.
About this Structure
2FHK is a Single protein structure of sequence from Methanopyrus kandleri with K and MFN as ligands. Active as Formylmethanofuran--tetrahydromethanopterin N-formyltransferase, with EC number 2.3.1.101 Full crystallographic information is available from OCA.
Reference
The structure of formylmethanofuran: tetrahydromethanopterin formyltransferase in complex with its coenzymes., Acharya P, Warkentin E, Ermler U, Thauer RK, Shima S, J Mol Biol. 2006 Mar 31;357(3):870-9. Epub 2006 Jan 23. PMID:16466742
Page seeded by OCA on Wed Nov 21 10:33:44 2007
