PDBsum entry 2o2k

Transferase

PDB id: 2o2k

Contents

Protein chain

332 a.a. *

Waters ×1195

* Residue conservation analysis

PDB id:

2o2k

Name:

Transferase

Title:

Crystal structure of the activation domain of human methionine synthase isoform/mutant d963e/k1071n

Structure:

Methionine synthase. Chain: a, b. Fragment: enzyme domain, residues 926-1265. Synonym: 5-methyltetrahydrofolate--homocysteine methyltransferase, methionine synthase, vitamin-b12 dependent, ms. Engineered: yes. Mutation: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: mtr. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.

Resolution:

1.60Å R-factor: 0.211 R-free: 0.248

Authors:

K.R.Wolthers,H.S.Toogood,T.A.Jowitt,K.R.Marshall,D.Leys,N.S.Scrutton

Key ref:

K.R.Wolthers et al. (2007). Crystal structure and solution characterization of the activation domain of human methionine synthase. Febs J, 274, 738-750. PubMed id: 17288554

Date:

30-Nov-06 Release date: 19-Dec-06

Protein chains

Q99707  (METH_HUMAN) -  Methionine synthase from Homo sapiens

Seq: 1265 a.a.

Struc: 332 a.a.*

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

Enzyme reactions

• Enzyme class: E.C.2.1.1.13 - methionine synthase.
• Pathway: Methionine Synthase
• Reaction: (6S)-5-methyl-5,6,7,8-tetrahydrofolate + L-homocysteine = (6S)-5,6,7,8- tetrahydrofolate + L-methionine
• Cofactor: Cob(II)alamin; Zn(2+)

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

reference

Febs J 274:738-750 (2007)

PubMed id: 17288554

Crystal structure and solution characterization of the activation domain of human methionine synthase.

K.R.Wolthers, H.S.Toogood, T.A.Jowitt, K.R.Marshall, D.Leys, N.S.Scrutton.

ABSTRACT

Human methionine synthase (hMS) is a multidomain cobalamin-dependent enzyme that catalyses the conversion of homocysteine to methionine by methyl group transfer. We report here the 1.6 A crystal structure of the C-terminal activation domain of hMS. The structure is C-shaped with the core comprising mixed alpha and beta regions, dominated by a twisted antiparallel beta sheet with a beta-meander region. These features, including the positions of the active-site residues, are similar to the activation domain of Escherichia coli cobalamin-dependent MS (MetH). Structural and solution studies suggest a small proportion of hMS activation domain exists in a dimeric form, which contrasts with the monomeric form of the E. coli homologue. Fluorescence studies show that human activation domain interacts with the FMN-binding domain of human methionine synthase reductase (hMSR). This interaction is enhanced in the presence of S-adenosyl-methionine. Binding of the D963E/K1071N mutant activation domain to the FMN domain of MSR is weaker than with wild-type activation domain. This suggests that one or both of the residues D963 and K1071 are important in partner binding. Key differences in the sequences and structures of hMS and MetH activation domains are recognized and include a major reorientation of an extended 3(10)-containing loop in the human protein. This structural alteration might reflect differences in their respective reactivation complexes and/or potential for dimer formation. The reported structure is a component of the multidomain hMS : MSR complex, and represents an important step in understanding the impact of clinical mutations and polymorphisms in this key electron transfer complex.