› 5v7i

X-ray diffraction
2.47Å resolution

Crystal structure of homo sapiens serine hydroxymethyltransferase 2 (mitochondrial) (SHMT2), in complex with glycine, PLP and folate-competitive pyrazolopyran inhibitor: 6-amino-4-isopropyl-3-methyl-4-(3-(pyrrolidin-1-yl)-5-(trifluoromethyl)phenyl)-1,4-dihydropyrano[2,3-c]pyrazole-5-carbonitrile

Released:
DOI: 10.2210/pdb5v7i/pdb
PDB entry 5v7i coloured by chain, front view.
PDB entry 5v7i coloured by chain, side view.
PDB entry 5v7i coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Human SHMT inhibitors reveal defective glycine import as a targetable metabolic vulnerability of diffuse large B-cell lymphoma.
Ducker GS, Ghergurovich JM, Mainolfi N, Suri V, Jeong SK, Hsin-Jung Li S, Friedman A, Manfredi MG, Gitai Z, Kim H, Rabinowitz JD
Proc Natl Acad Sci U S A 114 11404-11409 (2017)
PMID: 29073064

Function and Biology Details

Reaction catalysed: 
5,10-methylenetetrahydrofolate + glycine + H(2)O = tetrahydrofolate + L-serine
Biochemical function:
Biological process:
Cellular component:
Sequence domains:

Structure analysis Details

Assembly composition:
homo dimer (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-152739 (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
Serine hydroxymethyltransferase, mitochondrial Chains: A, B
Molecule details ›
Chains: A, B
Length: 476 amino acids
Theoretical weight: 52.94 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli
UniProt:
  • Canonical: P34897 (Residues: 29-504; Coverage: 94%)
Gene name: SHMT2
Sequence domains: Serine hydroxymethyltransferase
Structure domains:

Ligands and Environments

4 bound ligands:
Ligand 8Z1 2 x 8Z1
Ligand GOL 2 x GOL
Ligand PEG 2 x PEG
Ligand GLY 1 x GLY
1 modified residue:
Ligand LLP 2 x LLP

Experiments and Validation Details

Entry percentile scores
X-ray source: APS BEAMLINE 22-ID
Spacegroup: P6522
Unit cell:
a: 160.14Å b: 160.14Å c: 210.1Å
α: 90° β: 90° γ: 120°
R-values:
R R work R free
0.204 0.202 0.238
Expression system: Escherichia coli

Quick links

Citations

44 review citations

Targeting cancer metabolism in the era of precision oncology.
Stine et al. (2022)
43 more

10 mentions without citation

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