› 6fyz

X-ray diffraction
2.15Å resolution

Development and characterization of a CNS-penetrant benzhydryl hydroxamic acid class IIa histone deacetylase inhibitor

Released:
DOI: 10.2210/pdb6fyz/pdb
PDB entry 6fyz coloured by chain, front view.
PDB entry 6fyz coloured by chain, side view.
PDB entry 6fyz coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Development and characterization of a CNS-penetrant benzhydryl hydroxamic acid class IIa histone deacetylase inhibitor.
Luckhurst CA, Aziz O, Beaumont V, Bürli RW, Breccia P, Maillard MC, Haughan AF, Lamers M, Leonard P, Matthews KL, Raphy G, Stott AJ, Munoz-Sanjuan I, Thomas B, Wall M, Wishart G, Yates D, Dominguez C
Bioorg Med Chem Lett 29 83-88 (2019)
PMID: 30463802

Function and Biology Details

Reaction catalysed: 
Hydrolysis of an N(6)-acetyl-lysine residue of a histone to yield a deacetylated histone
Biochemical function:
  • not assigned
Biological process:
  • not assigned
Cellular component:
  • not assigned
Sequence domains:

Structure analysis Details

Assembly composition:
monomeric (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-157479 (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
Histone deacetylase 4 Chains: A, B, C
Molecule details ›
Chains: A, B, C
Length: 395 amino acids
Theoretical weight: 42.8 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli
UniProt:
  • Canonical: P56524 (Residues: 648-1033; Coverage: 36%)
Gene names: HDAC4, KIAA0288
Sequence domains: Histone deacetylase domain
Structure domains: Histone deacetylase domain

Ligands and Environments

3 bound ligands:
Ligand EBE 3 x EBE
Ligand ZN 6 x ZN
Ligand NA 3 x NA
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: DIAMOND BEAMLINE I04
Spacegroup: P32
Unit cell:
a: 105.53Å b: 105.53Å c: 88.86Å
α: 90° β: 90° γ: 120°
R-values:
R R work R free
0.194 0.193 0.228
Expression system: Escherichia coli

Quick links

Citations

2 review citations

PROTAC chemical probes for histone deacetylase enzymes.
Patel et al. (2023)
1 more

3 mentions without citation

Developing HDAC4-Selective Protein Degraders To Investigate the Role of HDAC4 in Huntington's Disease Pathology.
Macabuag et al. (2022)
2 more