Document Detail

Crystal structure of human histone lysine-specific demethylase 1 (LSD1).
MedLine Citation:
PMID:  16956976     Owner:  NLM     Status:  MEDLINE    
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.
Yong Chen; Yuting Yang; Feng Wang; Ke Wan; Kenichi Yamane; Yi Zhang; Ming Lei
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2006-09-06
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  103     ISSN:  0027-8424     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  2006 Sep 
Date Detail:
Created Date:  2006-09-20     Completed Date:  2006-12-14     Revised Date:  2013-06-07    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  13956-61     Citation Subset:  IM    
Department of Biological Chemistry, University of Michigan Medical School, 5413 Medical Science I, 1301 Catherine Road, Ann Arbor, MI 48109-0606, USA.
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MeSH Terms
Catalytic Domain
Crystallography, X-Ray
Histone Demethylases
Histones / metabolism
Models, Molecular
Molecular Sequence Data
Oxidoreductases, N-Demethylating / chemistry*,  genetics,  metabolism
Protein Structure, Tertiary*
Sequence Alignment
Grant Support
Reg. No./Substance:
0/Histones; EC 1.14.11.-/Histone Demethylases; EC 1.5.-/KDM1A protein, human; EC 1.5.-/Oxidoreductases, N-Demethylating

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