› 5lhh

X-ray diffraction
3.05Å resolution

Structure of the KDM1A/CoREST complex with the inhibitor 4-ethyl-N-[3-(methoxymethyl)-2-[[4-[[(3R)-pyrrolidin-3-yl]methoxy]phenoxy]methyl]phenyl]thieno[3,2-b]pyrrole-5-carboxamide

Released:
DOI: 10.2210/pdb5lhh/pdb
PDB entry 5lhh coloured by chain, front view.
PDB entry 5lhh coloured by chain, side view.
PDB entry 5lhh coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Thieno[3,2-b]pyrrole-5-carboxamides as New Reversible Inhibitors of Histone Lysine Demethylase KDM1A/LSD1. Part 2: Structure-Based Drug Design and Structure-Activity Relationship.
Vianello P, Sartori L, Amigoni F, Cappa A, Fagá G, Fattori R, Legnaghi E, Ciossani G, Mattevi A, Meroni G, Moretti L, Cecatiello V, Pasqualato S, Romussi A, Thaler F, Trifiró P, Villa M, Botrugno OA, Dessanti P, Minucci S, Vultaggio S, Zagarrí E, Varasi M, Mercurio C
J Med Chem 60 1693-1715 (2017)
PMID: 28186757

Function and Biology Details

Reaction catalysed: 
(1a) a [histone H3]-N(6),N(6)-dimethyl-L-lysine(4) + acceptor + H(2)O = a [histone H3]-N(6)-methyl-L-lysine(4) + formaldehyde + reduced acceptor
Biochemical function:
Biological process:
Cellular component:
Sequence domains:

Structure analysis Details

Assembly composition:
hetero dimer (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-129967 (preferred)
Entry contents:
2 distinct polypeptide molecules
Macromolecules (2 distinct):
Lysine-specific histone demethylase 1A Chain: A
Molecule details ›
Chain: A
Length: 852 amino acids
Theoretical weight: 93.01 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli
UniProt:
  • Canonical: O60341 (Residues: 1-852; Coverage: 100%)
Gene names: AOF2, KDM1, KDM1A, KIAA0601, LSD1
Sequence domains:
Structure domains:
REST corepressor 1 Chain: B
Molecule details ›
Chain: B
Length: 482 amino acids
Theoretical weight: 53.1 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli
UniProt:
  • Canonical: Q9UKL0 (Residues: 4-485; Coverage: 99%)
Gene names: KIAA0071, RCOR, RCOR1
Sequence domains:
Structure domains: Methane Monooxygenase Hydroxylase; Chain G, domain 1

Ligands and Environments

3 bound ligands:
Ligand FAD 1 x FAD
Ligand GOL 6 x GOL
Ligand 6X0 1 x 6X0
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: SLS BEAMLINE X06DA
Spacegroup: I222
Unit cell:
a: 120.49Å b: 179.93Å c: 234.44Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.16 0.159 0.186
Expression system: Escherichia coli

Quick links

Citations

7 review citations

LSD1/KDM1A inhibitors in clinical trials: advances and prospects.
Fang et al. (2019)
6 more

4 mentions without citation

Crystal Structure of LSD1 in Complex with 4-[5-(Piperidin-4-ylmethoxy)-2-(p-tolyl)pyridin-3-yl]benzonitrile.
Niwa et al. (2018)
3 more