› 1dia

X-ray diffraction
2.2Å resolution

HUMAN METHYLENETETRAHYDROFOLATE DEHYDROGENASE / CYCLOHYDROLASE COMPLEXED WITH NADP AND INHIBITOR LY249543

Released:
DOI: 10.2210/pdb1dia/pdb
PDB entry 1dia coloured by chain, front view.
PDB entry 1dia coloured by chain, side view.
PDB entry 1dia coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Structures of three inhibitor complexes provide insight into the reaction mechanism of the human methylenetetrahydrofolate dehydrogenase/cyclohydrolase.
Schmidt A, Wu H, MacKenzie RE, Chen VJ, Bewly JR, Ray JE, Toth JE, Cygler M
Biochemistry 39 6325-35 (2000)
PMID: 10828945

Function and Biology Details

Reactions catalysed: 
5,10-methylenetetrahydrofolate + NADP(+) = 5,10-methenyltetrahydrofolate + NADPH
5,10-methenyltetrahydrofolate + H(2)O = 10-formyltetrahydrofolate
ATP + formate + tetrahydrofolate = ADP + phosphate + 10-formyltetrahydrofolate
Biochemical function:
Biological process:
  • not assigned
Cellular component:
  • not assigned
Sequence domains:
Structure domains:

Structure analysis Details

Assembly composition:
homo dimer (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-145878 (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
C-1-tetrahydrofolate synthase, cytoplasmic, N-terminally processed Chains: A, B
Molecule details ›
Chains: A, B
Length: 306 amino acids
Theoretical weight: 33.34 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli
UniProt:
  • Canonical: P11586 (Residues: 1-306; Coverage: 33%)
Gene names: MTHFC, MTHFD, MTHFD1
Sequence domains:
Structure domains:

Ligands and Environments


Cofactor: Ligand NAP 2 x NAP
1 bound ligand:
Ligand L24 1 x L24
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: NSLS BEAMLINE X8C
Spacegroup: P212121
Unit cell:
a: 67.871Å b: 136.396Å c: 61.649Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.227 0.227 0.264
Expression system: Escherichia coli

Quick links

Citations

5 review citations

Acetogenesis and the Wood-Ljungdahl pathway of CO(2) fixation.
Ragsdale et al. (2008)
4 more

6 mentions without citation

A Review of Small-Molecule Inhibitors of One-Carbon Enzymes: SHMT2 and MTHFD2 in the Spotlight.
Cuthbertson et al. (2021)
5 more