2HKO

Crystal structure of LSD1

Summary for 2HKO

• Entry DOI: 10.2210/pdb2hko/pdb
• Descriptor: Lysine-specific histone demethylase 1, FLAVIN-ADENINE DINUCLEOTIDE (3 entities in total)
• Functional Keywords: swirm domain, fad binding domain, coiled-coil, amine oxidase domain, oxidoreductase
• Biological source: Homo sapiens (human)
• Cellular location: Nucleus: O60341
• Total number of polymer chains: 1
• Total formula weight: 74673.00

Authors

Chen, Y.,Yang, Y.T.,Wang, F.,Yanane, K.,Zhang, Y.,Lei, M. (deposition date: 2006-07-05, release date: 2006-08-29, Last modification date: 2024-02-14)

Primary citation

Chen, Y.,Yang, Y.,Wang, F.,Wan, K.,Yamane, K.,Zhang, Y.,Lei, M.
Crystal structure of human histone lysine-specific demethylase 1 (LSD1).
Proc.Natl.Acad.Sci.Usa, 103:13956-13961, 2006

PubMed Abstract: Lysine-specific demethylase 1 (LSD1) was recently identified as the first histone demethylase that specifically demethylates monomethylated and dimethylated histone H3 at K4. It is a component of the CoREST and other corepressor complexes and plays an important role in silencing neuronal-specific genes in nonneuronal cells, but the molecular mechanisms of its action remain unclear. The 2.8-A-resolution crystal structure of the human LSD1 reveals that LSD1 defines a new subfamily of FAD-dependent oxidases. The active center of LSD1 is characterized by a remarkable 1,245-A3 substrate-binding cavity with a highly negative electrostatic potential. Although the protein core of LSD1 resembles other flavoenzymes, its enzymatic activity and functions require two additional structural modules: an N-terminal SWIRM domain important for protein stability and a large insertion in the catalytic domain indispensable both for the demethylase activity and the interaction with CoREST. These results provide a framework for further probing the catalytic mechanism and the functional roles of LSD1.

PubMed: 16956976
DOI: 10.1073/pnas.0606381103

Experimental method

X-RAY DIFFRACTION (2.8 Å)