› 7o2i

X-ray diffraction
3Å resolution

METTL3-METTL14 heterodimer bound to the SAM competitive small molecule inhibitor STM2457

Released:
DOI: 10.2210/pdb7o2i/pdb
PDB entry 7o2i coloured by chain, front view.
PDB entry 7o2i coloured by chain, side view.
PDB entry 7o2i coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Small-molecule inhibition of METTL3 as a strategy against myeloid leukaemia.
Yankova E, Blackaby W, Albertella M, Rak J, De Braekeleer E, Tsagkogeorga G, Pilka ES, Aspris D, Leggate D, Hendrick AG, Webster NA, Andrews B, Fosbeary R, Guest P, Irigoyen N, Eleftheriou M, Gozdecka M, Dias JML, Bannister AJ, Vick B, Jeremias I, Vassiliou GS, Rausch O, Tzelepis K, Kouzarides T
Nature 593 597-601 (2021)
PMID: 33902106

Function and Biology Details

Reaction catalysed: 
S-adenosyl-L-methionine + adenine in mRNA = S-adenosyl-L-homocysteine + N(6)-methyladenine in mRNA
Biochemical function:
Biological process:
Cellular component:
Sequence domains:

Structure analysis Details

Assembly composition:
hetero dimer (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-183176 (preferred)
Entry contents:
2 distinct polypeptide molecules
Macromolecules (2 distinct):
N6-adenosine-methyltransferase catalytic subunit Chain: A
Molecule details ›
Chain: A
Length: 228 amino acids
Theoretical weight: 26.02 KDa
Source organism: Homo sapiens
Expression system: Spodoptera frugiperda
UniProt:
  • Canonical: Q86U44 (Residues: 353-580; Coverage: 39%)
Gene names: METTL3, MTA70
Sequence domains: MT-A70
N6-adenosine-methyltransferase non-catalytic subunit Chain: B
Molecule details ›
Chain: B
Length: 291 amino acids
Theoretical weight: 33.63 KDa
Source organism: Homo sapiens
Expression system: Spodoptera frugiperda
UniProt:
  • Canonical: Q9HCE5 (Residues: 107-395; Coverage: 63%)
Gene names: KIAA1627, METTL14
Sequence domains: MT-A70

Ligands and Environments

2 bound ligands:
Ligand V22 1 x V22
Ligand DMS 1 x DMS
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: DIAMOND BEAMLINE I04
Spacegroup: P3221
Unit cell:
a: 64.094Å b: 64.094Å c: 225.302Å
α: 90° β: 90° γ: 120°
R-values:
R R work R free
0.189 0.186 0.263
Expression system: Spodoptera frugiperda

Quick links

Citations

144 review citations

m6A modification: recent advances, anticancer targeted drug discovery and beyond.
Deng et al. (2022)
143 more

4 mentions without citation

METTL3 from Target Validation to the First Small-Molecule Inhibitors: A Medicinal Chemistry Journey.
Fiorentino et al. (2023)
3 more