› 8e9f

X-ray diffraction
1.55Å resolution

WD repeat-containing protein 5 complexed with 4-(7-((1H-imidazol-1-yl)methyl)-5-(1-methyl-3-(trifluoromethyl)-1H-pyrazol-4-yl)-1-oxo-3,4-dihydroisoquinolin-2(1H)-yl)-6-ethyl-N-methylquinoline-8-carboxamide (compound 10)

Released:
DOI: 10.2210/pdb8e9f/pdb
PDB entry 8e9f coloured by chain, front view.
PDB entry 8e9f coloured by chain, side view.
PDB entry 8e9f coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Structure-based discovery of potent WD repeat domain 5 inhibitors that demonstrate efficacy and safety in preclinical animal models.
Teuscher KB, Chowdhury S, Meyers KM, Tian J, Sai J, Van Meveren M, South TM, Sensintaffar JL, Rietz TA, Goswami S, Wang J, Grieb BC, Lorey SL, Howard GC, Liu Q, Moore WJ, Stott GM, Tansey WP, Lee T, Fesik SW
Proc Natl Acad Sci U S A 120 e2211297120 (2023)
PMID: 36574664

Function and Biology Details

Biochemical function:
Biological process:
Cellular component:
Sequence domains:

Structure analysis Details

Assembly composition:
monomeric (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-158474 (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
WD repeat-containing protein 5 Chain: A
Molecule details ›
Chain: A
Length: 305 amino acids
Theoretical weight: 33.59 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli
UniProt:
  • Canonical: P61964 (Residues: 30-334; Coverage: 91%)
Gene names: BIG3, WDR5
Sequence domains: WD domain, G-beta repeat

Ligands and Environments

2 bound ligands:
Ligand BEN 1 x BEN
Ligand UY9 1 x UY9
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: APS BEAMLINE 21-ID-G
Spacegroup: P21212
Unit cell:
a: 81.361Å b: 86.04Å c: 41.032Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.16 0.159 0.184
Expression system: Escherichia coli

Quick links

Citations

3 review citations

Recent Progress in Modulation of WD40-Repeat Domain 5 Protein (WDR5): Inhibitors and Degraders.
Gurung et al. (2023)
2 more

1 mention without citation

Structure-based discovery of potent WD repeat domain 5 inhibitors that demonstrate efficacy and safety in preclinical animal models.
Teuscher et al. (2023)