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2hko

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==Overview==
==Overview==
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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.
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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.
==About this Structure==
==About this Structure==
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[[Category: Wang, F.]]
[[Category: Wang, F.]]
[[Category: Yanane, K.]]
[[Category: Yanane, K.]]
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[[Category: Yang, Y.T.]]
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[[Category: Yang, Y T.]]
[[Category: Zhang, Y.]]
[[Category: Zhang, Y.]]
[[Category: FAD]]
[[Category: FAD]]
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[[Category: swirm domain]]
[[Category: swirm domain]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri Feb 15 17:32:30 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:42:51 2008''

Revision as of 15:42, 21 February 2008


2hko, resolution 2.80Å

Drag the structure with the mouse to rotate

Crystal structure of LSD1

Overview

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.

About this Structure

2HKO is a Single protein structure of sequence from Homo sapiens with as ligand. Full crystallographic information is available from OCA.

Reference

Crystal structure of human histone lysine-specific demethylase 1 (LSD1)., Chen Y, Yang Y, Wang F, Wan K, Yamane K, Zhang Y, Lei M, Proc Natl Acad Sci U S A. 2006 Sep 19;103(38):13956-61. Epub 2006 Sep 6. PMID:16956976

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