PDBsum entry: 1zrq

Oxidoreductase

PDB id: 1zrq

Contents

Protein chains

281 a.a. *

Ligands

SO4 ×4

FAD ×3

NAD ×3

Waters ×262

* Residue conservation analysis

PDB id:

1zrq

Name:

Oxidoreductase

Title:

Escherichia coli methylenetetrahydrofolate reductase (reduce complexed with nadh, ph 6.0

Structure:

5,10-methylenetetrahydrofolate reductase. Chain: a, b, c. Engineered: yes

Source:

Escherichia coli. Organism_taxid: 562. Gene: metf. Expressed in: escherichia coli. Expression_system_taxid: 562.

Biol. unit:

Hexamer (from PDB file)

Resolution:

2.20Å R-factor: 0.219 R-free: 0.252

Authors:

R.Pejchal,R.Sargeant,M.L.Ludwig

Key ref:

R.Pejchal et al. (2005). Structures of NADH and CH3-H4folate complexes of Escherichia coli methylenetetrahydrofolate reductase reveal a spartan strategy for a ping-pong reaction. Biochemistry, 44, 11447-11457. PubMed id: 16114881 DOI: 10.1021/bi050533q

Date:

19-May-05 Release date: 09-Aug-05

Protein chains

P0AEZ1  (METF_ECOLI) -  5,10-methylenetetrahydrofolate reductase

Seq: 296 a.a.

Struc: 281 a.a.

Enzyme reactions

• Enzyme class: E.C.1.5.1.20 - Methylenetetrahydrofolate reductase (NAD(P)H).
• Pathway: Folate Coenzymes
• Reaction: 5-methyltetrahydrofolate + NAD(P)(+) = 5,10-methylenetetrahydrofolate + NAD(P)H

5-methyltetrahydrofolate + NAD(P)(+) (Bound ligand (Het Group name = NAD) matches with 91.67% similarity) = 5,10-methylenetetrahydrofolate + NAD(P)H

• Cofactor: FAD

FAD (Bound ligand (Het Group name = FAD) corresponds exactly)

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

 Gene Ontology (GO) functional annotation 

• Biological process: oxidation-reduction process (4 terms)
• Biochemical function: oxidoreductase activity (2 terms)

reference

DOI no: 10.1021/bi050533q

Biochemistry 44:11447-11457 (2005)

PubMed id: 16114881

Structures of NADH and CH3-H4folate complexes of Escherichia coli methylenetetrahydrofolate reductase reveal a spartan strategy for a ping-pong reaction.

R.Pejchal, R.Sargeant, M.L.Ludwig.

ABSTRACT

Methylenetetrahydrofolate reductases (MTHFRs; EC 1.7.99.5) catalyze the NAD(P)H-dependent reduction of 5,10-methylenetetrahydrofolate (CH(2)-H(4)folate) to 5-methyltetrahydrofolate (CH(3)-H(4)folate) using flavin adenine dinucleotide (FAD) as a cofactor. The initial X-ray structure of Escherichia coli MTHFR revealed that this 33-kDa polypeptide is a (betaalpha)(8) barrel that aggregates to form an unusual tetramer with only 2-fold symmetry. Structures of reduced enzyme complexed with NADH and of oxidized Glu28Gln enzyme complexed with CH(3)-H(4)folate have now been determined at resolutions of 1.95 and 1.85 A, respectively. The NADH complex reveals a rare mode of dinucleotide binding; NADH adopts a hairpin conformation and is sandwiched between a conserved phenylalanine, Phe223, and the isoalloxazine ring of FAD. The nicotinamide of the bound pyridine nucleotide is stacked against the si face of the flavin ring with C4 adjoining the N5 of FAD, implying that this structure models a complex that is competent for hydride transfer. In the complex with CH(3)-H(4)folate, the pterin ring is also stacked against FAD in an orientation that is favorable for hydride transfer. Thus, the binding sites for the two substrates overlap, as expected for many enzymes that catalyze ping-pong reactions, and several invariant residues interact with both folate and pyridine nucleotide substrates. Comparisons of liganded and substrate-free structures reveal multiple conformations for the loops beta2-alpha2 (L2), beta3-alpha3 (L3), and beta4-alpha4 (L4) and suggest that motions of these loops facilitate the ping-pong reaction. In particular, the L4 loop adopts a "closed" conformation that allows Asp120 to hydrogen bond to the pterin ring in the folate complex but must move to an "open" conformation to allow NADH to bind.