› 7zuy

X-ray diffraction
2Å resolution

HUMAN PRMT5:MEP50 Crystal Structure With MTA and Fragment Bound

Released:
DOI: 10.2210/pdb7zuy/pdb
PDB entry 7zuy coloured by chain, front view.
PDB entry 7zuy coloured by chain, side view.
PDB entry 7zuy coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Fragment optimization and elaboration strategies - the discovery of two lead series of PRMT5/MTA inhibitors from five fragment hits.
Smith CR, Kulyk S, Ahmad MUD, Arkhipova V, Christensen JG, Gunn RJ, Ivetac A, Ketcham JM, Kuehler J, Lawson JD, Thomas NC, Wang X, Marx MA
OpenAccess logo RSC Med Chem 13 1549-1564 (2022)
PMID: 36545438

Function and Biology Details

Reaction catalysed: 
(1a) S-adenosyl-L-methionine + [protein]-L-arginine = S-adenosyl-L-homocysteine + [protein]-N(omega)-methyl-L-arginine
Biochemical function:
Biological process:
Cellular component:
Sequence domains:

Structure analysis Details

Assembly composition:
hetero dimer (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-127075 (preferred)
Entry contents:
2 distinct polypeptide molecules
Macromolecules (2 distinct):
Protein arginine N-methyltransferase 5 Chain: A
Molecule details ›
Chain: A
Length: 645 amino acids
Theoretical weight: 73.76 KDa
Source organism: Homo sapiens
Expression system: Spodoptera frugiperda
UniProt:
  • Canonical: O14744 (Residues: 2-637; Coverage: 100%)
Gene names: HRMT1L5, IBP72, JBP1, PRMT5, SKB1
Sequence domains:
Methylosome protein WDR77 Chain: B
Molecule details ›
Chain: B
Length: 350 amino acids
Theoretical weight: 37.86 KDa
Source organism: Homo sapiens
Expression system: Spodoptera frugiperda
UniProt:
  • Canonical: Q9BQA1 (Residues: 2-342; Coverage: 100%)
Gene names: HKMT1069, MEP50, Nbla10071, WD45, WDR77
Sequence domains: WD domain, G-beta repeat

Ligands and Environments

3 bound ligands:
Ligand MTA 1 x MTA
Ligand UNL 1 x UNL
Ligand GOL 2 x GOL
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: DIAMOND BEAMLINE I03
Spacegroup: I222
Unit cell:
a: 105.262Å b: 139.037Å c: 178.421Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.224 0.222 0.27
Expression system: Spodoptera frugiperda

Quick links

Citations

1 mention without citation

Fragment optimization and elaboration strategies - the discovery of two lead series of PRMT5/MTA inhibitors from five fragment hits.
Smith et al. (2022)