3ZN1: Lsd1-corest In Complex With Prlylv Peptide

The combinatorial assembly of protein complexes is at the heart of chromatin biology. Lysine demethylase LSD1(KDM1A)/CoREST beautifully exemplifies this concept. The active site of the enzyme tightly associates to the N-terminal domain of transcription factors of the SNAIL1 family, which therefore can competitively inhibit the binding of the N-terminal tail of the histone substrate. Our enzymatic, crystallographic, spectroscopic, and computational studies reveal that LSD1/CoREST can bind to a hexapeptide derived from the SNAIL sequence through recognition of a positively charged alpha-helical turn that forms upon binding to the enzyme. Variations in sequence and length of this six amino acid ligand modulate affinities enabling the same binding site to differentially interact with proteins that exert distinct biological functions. The discovered short peptide inhibitors exhibit antiproliferative activities and lay the foundation for the development of peptidomimetic small molecule inhibitors of LSD1.
PDB ID: 3ZN1Download
MMDB ID: 110824
PDB Deposition Date: 2013/2/13
Updated in MMDB: 2013/08
Experimental Method:
x-ray diffraction
Resolution: 3.1  Å
Source Organism:
Similar Structures:
Biological Unit for 3ZN1: trimeric; determined by software (PISA)
Molecular Components in 3ZN1
Label Count Molecule
Proteins (3 molecules)
Lysine-specific Histone Demethylase 1A(Gene symbol: KDM1A)
Molecule annotation
Rest Corepressor 1(Gene symbol: RCOR1)
Molecule annotation
Molecule annotation
Chemical (1 molecule)
* Click molecule labels to explore molecular sequence information.

Citing MMDB