› 6jib

X-ray diffraction
2.25Å resolution

Human MTHFD2 in complex with DS44960156

Released:
DOI: 10.2210/pdb6jib/pdb
PDB entry 6jib coloured by chain, front view.
PDB entry 6jib coloured by chain, side view.
PDB entry 6jib coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Structure-Based Design and Synthesis of an Isozyme-Selective MTHFD2 Inhibitor with a Tricyclic Coumarin Scaffold.
Kawai J, Ota M, Ohki H, Toki T, Suzuki M, Shimada T, Matsui S, Inoue H, Sugihara C, Matsuhashi N, Matsui Y, Takaishi S, Nakayama K
ACS Med Chem Lett 10 893-898 (2019)
PMID: 31223444

Function and Biology Details

Reactions catalysed: 
5,10-methylenetetrahydrofolate + NAD(+) = 5,10-methenyltetrahydrofolate + NADH
5,10-methenyltetrahydrofolate + H(2)O = 10-formyltetrahydrofolate
Biochemical function:
Biological process:
  • not assigned
Cellular component:
  • not assigned
Sequence domains:

Structure analysis Details

Assembly composition:
homo dimer (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-146835 (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
Bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase, mitochondrial Chains: A, B
Molecule details ›
Chains: A, B
Length: 323 amino acids
Theoretical weight: 35.22 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli
UniProt:
  • Canonical: P13995 (Residues: 36-338; Coverage: 87%)
  • Best match: P13995-2 (Residues: 1-236)
Gene names: MTHFD2, NMDMC
Sequence domains:

Ligands and Environments

3 bound ligands:
Ligand BQF 4 x BQF
Ligand PO4 2 x PO4
Ligand GOL 5 x GOL
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: PHOTON FACTORY BEAMLINE AR-NW12A
Spacegroup: P65
Unit cell:
a: 116.424Å b: 116.424Å c: 113.178Å
α: 90° β: 90° γ: 120°
R-values:
R R work R free
0.203 0.201 0.243
Expression system: Escherichia coli

Quick links

Citations

5 review citations

More Than a Metabolic Enzyme: MTHFD2 as a Novel Target for Anticancer Therapy?
Zhu et al. (2020)
4 more

5 mentions without citation

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