› 6ckc

X-ray diffraction
2.8Å resolution

Structure of PRMT5:MEP50 in complex with LLY-283, a potent and selective inhibitor of PRMT5, with antitumor activity

Released:
DOI: 10.2210/pdb6ckc/pdb
PDB entry 6ckc coloured by chain, front view.
PDB entry 6ckc coloured by chain, side view.
PDB entry 6ckc coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
LLY-283, a Potent and Selective Inhibitor of Arginine Methyltransferase 5, PRMT5, with Antitumor Activity.
Bonday ZQ, Cortez GS, Grogan MJ, Antonysamy S, Weichert K, Bocchinfuso WP, Li F, Kennedy S, Li B, Mader MM, Arrowsmith CH, Brown PJ, Eram MS, Szewczyk MM, Barsyte-Lovejoy D, Vedadi M, Guccione E, Campbell RM
ACS Med Chem Lett 9 612-617 (2018)
PMID: 30034588

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 octamer (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-127081 (preferred)
Entry contents:
2 distinct polypeptide molecules
Macromolecules (2 distinct):
Protein arginine N-methyltransferase 5 Chain: A
Molecule details ›
Chain: A
Length: 650 amino acids
Theoretical weight: 74.28 KDa
Source organism: Homo sapiens
Expression system: Spodoptera frugiperda
UniProt:
  • Canonical: O14744 (Residues: 1-637; Coverage: 100%)
Gene names: HRMT1L5, IBP72, JBP1, PRMT5, SKB1
Sequence domains:
Structure domains:
Methylosome protein WDR77 Chain: B
Molecule details ›
Chain: B
Length: 344 amino acids
Theoretical weight: 36.88 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
Structure domains: YVTN repeat-like/Quinoprotein amine dehydrogenase

Ligands and Environments

1 bound ligand:
Ligand F5J 1 x F5J
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: CLSI BEAMLINE 08ID-1
Spacegroup: I222
Unit cell:
a: 102.785Å b: 139.077Å c: 178.961Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.18 0.178 0.214
Expression system: Spodoptera frugiperda

Quick links

Citations

23 review citations

Protein arginine methylation: from enigmatic functions to therapeutic targeting.
Wu et al. (2021)
22 more

10 mentions without citation

Protein arginine methyltransferases: insights into the enzyme structure and mechanism at the atomic level.
Tewary et al. (2019)
9 more