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PDBsum entry 2ejr
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Oxidoreductase
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PDB id
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2ejr
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Contents |
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* Residue conservation analysis
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Enzyme class:
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E.C.1.14.99.66
- [histone-H3]-N(6),N(6)-dimethyl-L-lysine(4) FAD-dependent demethylase.
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Reaction:
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N6,N6-dimethyl-L-lysyl4-[histone H3] + 2 A + 2 H2O = L-lysyl4- [histone H3] + 2 formaldehyde + 2 AH2
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N(6),N(6)-dimethyl-L-lysyl(4)-[histone H3]
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+
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2
×
A
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+
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2
×
H2O
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=
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L-lysyl(4)- [histone H3]
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+
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2
×
formaldehyde
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+
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2
×
AH2
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Molecule diagrams generated from .mol files obtained from the
KEGG ftp site
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Biochem Biophys Res Commun
366:15-22
(2008)
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PubMed id:
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Crystal structure of histone demethylase LSD1 and tranylcypromine at 2.25 A.
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S.Mimasu,
T.Sengoku,
S.Fukuzawa,
T.Umehara,
S.Yokoyama.
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ABSTRACT
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Transcriptional activity and chromatin structure accessibility are correlated
with the methylation of specific histone residues. Lysine-specific demethylase 1
(LSD1) is the first discovered histone demethylase, which demethylates Lys4 or
Lys9 of histone H3, using FAD. Among the known monoamine oxidase inhibitors,
tranylcypromine (Parnate) showed the most potent inhibitory effect on LSD1.
Recently, the crystal structure of LSD1 and tranylcypromine was solved at 2.75
A, revealing a five-membered ring fused to the flavin of LSD1. In this study, we
refined the crystal structure of the LSD1-tranylcypromine complex to 2.25 A. The
five-membered ring model did not fit completely with the electron density,
giving R(work)/R(free) values of 0.226/0.254. On the other hand, the N(5) adduct
gave the lowest R(work)/R(free) values of 0.218/0.248, among the tested models.
These results imply that the LSD1-tranylcypromine complex is not completely
composed of the five-membered adduct, but partially contains an intermediate,
such as the N(5) adduct.
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Literature references that cite this PDB file's key reference
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PubMed id
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Reference
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S.Hayami,
J.D.Kelly,
H.S.Cho,
M.Yoshimatsu,
M.Unoki,
T.Tsunoda,
H.I.Field,
D.E.Neal,
H.Yamaue,
B.A.Ponder,
Y.Nakamura,
and
R.Hamamoto
(2011).
Overexpression of LSD1 contributes to human carcinogenesis through chromatin regulation in various cancers.
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Int J Cancer,
128,
574-586.
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M.L.Bellows,
and
C.A.Floudas
(2010).
Computational methods for de novo protein design and its applications to the human immunodeficiency virus 1, purine nucleoside phosphorylase, ubiquitin specific protease 7, and histone demethylases.
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Curr Drug Targets,
11,
264-278.
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A.Karytinos,
F.Forneris,
A.Profumo,
G.Ciossani,
E.Battaglioli,
C.Binda,
and
A.Mattevi
(2009).
A novel mammalian flavin-dependent histone demethylase.
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J Biol Chem,
284,
17775-17782.
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F.Forneris,
C.Binda,
E.Battaglioli,
and
A.Mattevi
(2008).
LSD1: oxidative chemistry for multifaceted functions in chromatin regulation.
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Trends Biochem Sci,
33,
181-189.
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P.A.Cole
(2008).
Chemical probes for histone-modifying enzymes.
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Nat Chem Biol,
4,
590-597.
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R.Gatta,
and
R.Mantovani
(2008).
NF-Y substitutes H2A-H2B on active cell-cycle promoters: recruitment of CoREST-KDM1 and fine-tuning of H3 methylations.
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Nucleic Acids Res,
36,
6592-6607.
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The most recent references are shown first.
Citation data come partly from CiteXplore and partly
from an automated harvesting procedure. Note that this is likely to be
only a partial list as not all journals are covered by
either method. However, we are continually building up the citation data
so more and more references will be included with time.
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Links
