PDBsum entry 1xr2

Transferase

PDB id: 1xr2

Contents

Protein chains

715 a.a. *

Ligands

SO4 ×2

C2F ×2

MRY ×2

Waters ×238

* Residue conservation analysis

PDB id:

1xr2

Name:

Transferase

Title:

Crystal structure of oxidized t. Maritima cobalamin-independent methionine synthase complexed with methyltetrahydrofolate

Structure:

5-methyltetrahydropteroyltriglutamate--homocysteine methyltransferase. Chain: a, b. Synonym: methionine synthase, vitamin-b12 independent isozyme, cobalamin-independent methionine synthase. Engineered: yes

Source:

Thermotoga maritima. Organism_taxid: 2336. Gene: mete. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

2.35Å R-factor: 0.207 R-free: 0.254

Authors:

R.Pejchal,M.L.Ludwig

Key ref:

R.Pejchal and M.L.Ludwig (2005). Cobalamin-independent methionine synthase (MetE): a face-to-face double barrel that evolved by gene duplication. Plos Biol, 3, e31-264. PubMed id: 15630480

Date:

13-Oct-04 Release date: 01-Mar-05

Protein chains

Q9X112  (METE_THEMA) -  5-methyltetrahydropteroyltriglutamate--homocysteine methyltransferase from Thermotoga maritima (strain ATCC 43589 / DSM 3109 / JCM 10099 / NBRC 100826 / MSB8)

Seq: 734 a.a.

Struc: 715 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

Enzyme reactions

• Enzyme class: E.C.2.1.1.14 - 5-methyltetrahydropteroyltriglutamate--homocysteine S-methyltransferase.
• Reaction: 5-methyltetrahydropteroyltri-L-glutamate + L-homocysteine = tetrahydropteroyltri-L-glutamate + L-methionine

5-methyltetrahydropteroyltri-L-glutamate (Bound ligand (Het Group name = C2F) matches with 61.54% similarity) + L-homocysteine (Bound ligand (Het Group name = MRY) matches with 45.45% similarity) = tetrahydropteroyltri-L-glutamate + L-methionine

• Cofactor: Zn(2+)

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

Plos Biol 3:e31-264 (2005)

PubMed id: 15630480

Cobalamin-independent methionine synthase (MetE): a face-to-face double barrel that evolved by gene duplication.

R.Pejchal, M.L.Ludwig.

ABSTRACT

Cobalamin-independent methionine synthase (MetE) catalyzes the transfer of a methyl group from methyltetrahydrofolate to L-homocysteine (Hcy) without using an intermediate methyl carrier. Although MetE displays no detectable sequence homology with cobalamin-dependent methionine synthase (MetH), both enzymes require zinc for activation and binding of Hcy. Crystallographic analyses of MetE from T. maritima reveal an unusual dual-barrel structure in which the active site lies between the tops of the two (betaalpha)(8) barrels. The fold of the N-terminal barrel confirms that it has evolved from the C-terminal polypeptide by gene duplication; comparisons of the barrels provide an intriguing example of homologous domain evolution in which binding sites are obliterated. The C-terminal barrel incorporates the zinc ion that binds and activates Hcy. The zinc-binding site in MetE is distinguished from the (Cys)(3)Zn site in the related enzymes, MetH and betaine-homocysteine methyltransferase, by its position in the barrel and by the metal ligands, which are histidine, cysteine, glutamate, and cysteine in the resting form of MetE. Hcy associates at the face of the metal opposite glutamate, which moves away from the zinc in the binary E.Hcy complex. The folate substrate is not intimately associated with the N-terminal barrel; instead, elements from both barrels contribute binding determinants in a binary complex in which the folate substrate is incorrectly oriented for methyl transfer. Atypical locations of the Hcy and folate sites in the C-terminal barrel presumably permit direct interaction of the substrates in a ternary complex. Structures of the binary substrate complexes imply that rearrangement of folate, perhaps accompanied by domain rearrangement, must occur before formation of a ternary complex that is competent for methyl transfer.