PDBsum entry 1f6y

Transferase

PDB id: 1f6y

Contents

Protein chains

258 a.a. *

Waters ×185

* Residue conservation analysis

References listed in PDB file

Key reference

• Title: Crystal structure of a methyltetrahydrofolate- And corrinoid-Dependent methyltransferase.
• Authors: T.Doukov, J.Seravalli, J.J.Stezowski, S.W.Ragsdale.
• Ref.: Structure, 2000, 8, 817-830. [DOI no: 10.1016/S0969-2126(00)00172-6]
• PubMed id: 10997901

Abstract

BACKGROUND: Methyltetrahydrofolate, corrinoid iron-sulfur protein methyltransferase (MeTr), catalyzes a key step in the Wood-Ljungdahl pathway of carbon dioxide fixation. It transfers the N5-methyl group from methyltetrahydrofolate (CH3-H4folate) to a cob(I)amide center in another protein, the corrinoid iron-sulfur protein. MeTr is a member of a family of proteins that includes methionine synthase and methanogenic enzymes that activate the methyl group of methyltetra-hydromethano(or -sarcino)pterin. We report the first structure of a protein in this family. RESULTS: We determined the crystal structure of MeTr from Clostridium thermoaceticum at 2.2 A resolution using multiwavelength anomalous diffraction methods. The overall architecture presents a new functional class of the versatile triose phosphate isomerase (TIM) barrel fold. The MeTr tertiary structure is surprisingly similar to the crystal structures of dihydropteroate synthetases despite sharing less than 20% sequence identity. This homology permitted the methyl-H4folate binding site to be modeled. The model suggests extensive conservation of the pterin ring binding residues in the polar active sites of the methyltransferases and dihydropteroate synthetases. The most significant structural difference between these enzymes is in a loop structure above the active site. It is quite open in MeTr, where it can be modeled as the cobalamin binding site. CONCLUSIONS: The MeTr structure consists of a TIM barrel that embeds methyl-H4folate and cobamide. All related methyltransferases are predicted to fold into a similar TIM barrel pattern and have a similar pterin and cobamide binding site. The observed structure is consistent with either a 'front' (N5) or 'back' (C8a) side protonation of CH3-H4folate, a key step that enhances the electrophilic character of the methyl group, activating it for nucleophilic attack by Co(I).

Figure 7.
Figure 7. Common structural arrangement for cobamide-dependent enzymes. (a). The cobalamin coordinates from the 1bmt structure were used to manually dock the cobalamin molecule into the TIM barrel cavity by avoiding van der Waals clashes, but minimizing N5 to Co distance. (b) Interactions between cobalamin and methylmalonyl-CoA mutase [59 and 60]. The figures were produced using QUANTA (Molecular Simulations Inc.).

The above figure is reprinted by permission from Cell Press: Structure (2000, 8, 817-830) copyright 2000.

Secondary reference #1

• Title: Preliminary X-Ray crystallographic study of methyltetrahydrofolate: corrinoid/iron sulfur protein methyltransferase from clostridium thermoaceticum.
• Authors: T.I.Doukov, S.Zhao, C.R.Ross, D.L.Roberts, J.J.Kim, S.W.Ragsdale, J.J.Stezowski.
• Ref.: Acta Crystallogr D Biol Crystallogr, 1995, 51, 1092-1093. [DOI no: 10.1107/S0907444995005403]
• PubMed id: 15299784

Figure 1.
Fig. 1. The reaction of MeTr.

The above figure is reproduced from the cited reference with permission from the IUCr

Secondary reference #2

• Title: The reductive acetyl coenzyme a pathway: sequence and heterologous expression of active methyltetrahydrofolate:corrinoid/iron-Sulfur protein methyltransferase from clostridium thermoaceticum.
• Authors: D.L.Roberts, S.Zhao, T.Doukov, S.W.Ragsdale.
• Ref.: J Bacteriol, 1994, 176, 6127-6130.
• PubMed id: 7928975

Secondary reference #3

• Title: Binding of (6r,S)-Methyltetrahydrofolate to methyltransferase from clostridium thermoaceticum: role of protonation of methyltetrahydrofolate in the mechanism of methyl transfer.
• Authors: J.Seravalli, R.K.Shoemaker, M.J.Sudbeck, S.W.Ragsdale.
• Ref.: Biochemistry, 1999, 38, 5736-5745. [DOI no: 10.1021/bi9824745]
• PubMed id: 10231524

Secondary reference #4

• Title: Mechanism of transfer of the methyl group from (6s)-Methyltetrahydrofolate to the corrinoid/iron-Sulfur protein catalyzed by the methyltransferase from clostridium thermoaceticum: a key step in the wood-Ljungdahl pathway of acetyl-Coa synthesis.
• Authors: J.Seravalli, S.Zhao, S.W.Ragsdale.
• Ref.: Biochemistry, 1999, 38, 5728-5735. [DOI no: 10.1021/bi982473c]
• PubMed id: 10231523