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› 4tn4

X-ray diffraction
2.2Å resolution

Crystal structure of ternary complex of Plasmodium vivax SHMT with glycine and a novel pyrazolopyran 33G: (4S)-6-amino-4-(5-cyano-3'-fluorobiphenyl-3-yl)-4-cyclobutyl-3-methyl-2,4-dihydropyrano[2,3-c]pyrazole-5-carbonitrile

Released:
DOI: 10.2210/pdb4tn4/pdb
Model geometry
Fit model/data
PDB entry 4tn4 coloured by chain, front view.
PDB entry 4tn4 coloured by chain, side view.
PDB entry 4tn4 coloured by chain, top view.
Source organism: Plasmodium vivax Sal-1
Primary publication:
Inhibitors of plasmodial serine hydroxymethyltransferase (SHMT): cocrystal structures of pyrazolopyrans with potent blood- and liver-stage activities.
Witschel MC, Rottmann M, Schwab A, Leartsakulpanich U, Chitnumsub P, Seet M, Tonazzi S, Schwertz G, Stelzer F, Mietzner T, McNamara C, Thater F, Freymond C, Jaruwat A, Pinthong C, Riangrungroj P, Oufir M, Hamburger M, Mäser P, Sanz-Alonso LM, Charman S, Wittlin S, Yuthavong Y, Chaiyen P, Diederich F
J Med Chem 58 3117-30 (2015)
PMID: 25785478

Function and Biology Details

Reaction catalysed: 
(6R)-5,10-methylene-5,6,7,8-tetrahydrofolate + glycine + H2O = (6S)-5,6,7,8-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-107691 (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
glycine hydroxymethyltransferase Chains: A, B, C
Molecule details ›
Chains: A, B, C
Length: 442 amino acids
Theoretical weight: 49.25 KDa
Source organism: Plasmodium vivax Sal-1
Expression system: Escherichia coli BL21(DE3)
UniProt:
  • Canonical: A5K8L9 (Residues: 1-442; Coverage: 100%)
Gene name: PVX_100730
Sequence domains: Serine hydroxymethyltransferase
Structure domains:

Ligands and Environments

4 bound ligands:
Ligand PLG 3 x PLG
Ligand BME 3 x BME
Ligand 33G 3 x 33G
Ligand CL 2 x CL
No modified residues

Experiments and Validation Details

wwPDB Validation report is not available for this entry.
X-ray source: NSRRC BEAMLINE BL13B1
Spacegroup: C2
Unit cell:
a: 100.412Å b: 57.989Å c: 236.955Å
α: 90° β: 89.99° γ: 90°
R-values:
R R work R free
0.224 0.217 0.286
Expression system: Escherichia coli BL21(DE3)

Quick links

Citations

6 review citations

Targeting mitochondrial metabolism for precision medicine in cancer.
Sainero-Alcolado et al. (2022)
5 more

1 mention without citation

Human DND1-RRM2 forms a non-canonical domain swapped dimer.
Kumari et al. (2021)