Lysine-specific histone demethylase

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== Relevance ==
== Relevance ==
LSD1 is a potential anti-tumor drug target since it inhibits the tumor suppressor p53<ref>PMID:22533360</ref>. LSD2 demethylation activity helps in increased binding of NF-kB and activation of several inflammatory genes<ref>PMID:20832726</ref>. LSD5B deficiency promotes DNA damage processes<ref>PMID:24778210</ref>.
LSD1 is a potential anti-tumor drug target since it inhibits the tumor suppressor p53<ref>PMID:22533360</ref>. LSD2 demethylation activity helps in increased binding of NF-kB and activation of several inflammatory genes<ref>PMID:20832726</ref>. LSD5B deficiency promotes DNA damage processes<ref>PMID:24778210</ref>.
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== Structural highlights ==
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LSD1 contains several domains: a flexible N-terminal domain, a SWIRM domain (an α-helical domain found in chromosomal proteins mediating protein-protein interactions in chromatin), a substrate and FAD-binding domain, a tower domain (a pair of 2 long anti-parallel helices supporting a 3-helix bundle) and a C-terminal domain<ref>PMID:16956976</ref>.
==3D structures of lysine-specific histone demethylase 1==
==3D structures of lysine-specific histone demethylase 1==

Revision as of 10:56, 13 April 2016

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Contents

Function

Lysine-specific histone demethylase 1 or 1A (LSD1) is a flavin-dependent oxidase that catalyzes the removal of methyl groups from mono- and dimethylated lysine 4 of histone H3. LSD1 is a nuclear homolog of amine oxidase. It functions as histone demethylase and transcriptional corepressor. LSD1 demethylation occurs via a reaction which produces formaldehyde. LSD1 is a component of transcriptional co-repressor complex which also contains CoREST (co-repressor of element-1-silencing transcription factor)[1].
Lysine-specific histone demethylase 2 or 1B (LSD2) is a flavin-dependent oxidase that catalyzes the removal of methyl groups from mono- and dimethylated lysine 9 of histone H3.
Lysine-specific histone demethylase 5B or KDM5B (LSD5B) is a JmjC domain containing histone demethylase and is an improtant component of DNA repair

Relevance

LSD1 is a potential anti-tumor drug target since it inhibits the tumor suppressor p53[2]. LSD2 demethylation activity helps in increased binding of NF-kB and activation of several inflammatory genes[3]. LSD5B deficiency promotes DNA damage processes[4].

Structural highlights

LSD1 contains several domains: a flexible N-terminal domain, a SWIRM domain (an α-helical domain found in chromosomal proteins mediating protein-protein interactions in chromatin), a substrate and FAD-binding domain, a tower domain (a pair of 2 long anti-parallel helices supporting a 3-helix bundle) and a C-terminal domain[5].

3D structures of lysine-specific histone demethylase 1

Updated on 13-April-2016

References

  1. ↑ Chen Y, Jie W, Yan W, Zhou K, Xiao Y. Lysine-specific histone demethylase 1 (LSD1): A potential molecular target for tumor therapy. Crit Rev Eukaryot Gene Expr. 2012;22(1):53-9. PMID:22339659
  2. ↑ Pollock JA, Larrea MD, Jasper JS, McDonnell DP, McCafferty DG. Lysine-specific histone demethylase 1 inhibitors control breast cancer proliferation in ERalpha-dependent and -independent manners. ACS Chem Biol. 2012 Jul 20;7(7):1221-31. doi: 10.1021/cb300108c. Epub 2012 May, 10. PMID:22533360 doi:http://dx.doi.org/10.1021/cb300108c
  3. ↑ van Essen D, Zhu Y, Saccani S. A feed-forward circuit controlling inducible NF-kappaB target gene activation by promoter histone demethylation. Mol Cell. 2010 Sep 10;39(5):750-60. doi: 10.1016/j.molcel.2010.08.010. PMID:20832726 doi:http://dx.doi.org/10.1016/j.molcel.2010.08.010
  4. ↑ Li X, Liu L, Yang S, Song N, Zhou X, Gao J, Yu N, Shan L, Wang Q, Liang J, Xuan C, Wang Y, Shang Y, Shi L. Histone demethylase KDM5B is a key regulator of genome stability. Proc Natl Acad Sci U S A. 2014 May 13;111(19):7096-101. doi:, 10.1073/pnas.1324036111. Epub 2014 Apr 28. PMID:24778210 doi:http://dx.doi.org/10.1073/pnas.1324036111
  5. ↑ 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 U S A. 2006 Sep 19;103(38):13956-61. Epub 2006 Sep 6. PMID:16956976

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