Lysine-specific histone demethylase
From Proteopedia
(Difference between revisions)
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== Function == | == Function == | ||
| - | '''Lysine-specific histone demethylase 1''' (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 | + | '''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)<ref>PMID:22339659</ref>.<br /> |
| + | '''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.<br /> | ||
| + | '''Lysine-specific histone demethylase 5B or KDM5B''' (LSD5B) is a JmjC domain containing histone demethylase and is an improtant component of DNA repair | ||
== Relevance == | == Relevance == | ||
| - | LSD1 is a potential anti-tumor drug target since it inhibits the tumor suppressor p53<ref>PMID:22533360</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>. |
==3D structures of lysine-specific histone demethylase 1== | ==3D structures of lysine-specific histone demethylase 1== | ||
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{{#tree:id=OrganizedByTopic|openlevels=0| | {{#tree:id=OrganizedByTopic|openlevels=0| | ||
| - | *lysine-specific histone demethylase | + | *lysine-specific histone demethylase 1 |
**[[2com]], [[2l3d]] - hLSD1 SWIRM domain – human – NMR<br /> | **[[2com]], [[2l3d]] - hLSD1 SWIRM domain – human – NMR<br /> | ||
**[[2h94]], [[2dw4]], [[2z3y]], [[2z5u]], [[4fwe]], [[4fwj]], [[4gu1]] – hLSD1<br /> | **[[2h94]], [[2dw4]], [[2z3y]], [[2z5u]], [[4fwe]], [[4fwj]], [[4gu1]] – hLSD1<br /> | ||
**[[2hko]] – hLSD1 (mutant)<br /> | **[[2hko]] – hLSD1 (mutant)<br /> | ||
| - | **[[2ma5]] – hLSD 5B zinc finger domain 3 - NMR<br /> | ||
| - | **[[2mny]] – hLSD 5B zinc finger domain 1 - NMR<br /> | ||
**[[2ejr]], [[3abt]], [[3abu]] – hLSD1 + tranylcypromine derivative<br /> | **[[2ejr]], [[3abt]], [[3abu]] – hLSD1 + tranylcypromine derivative<br /> | ||
**[[4gut]], [[4guu]] – hLSD1 + oxidoreductase<br /> | **[[4gut]], [[4guu]] – hLSD1 + oxidoreductase<br /> | ||
| - | * | + | *LSD1 complex with histone H3 peptide |
| - | **[[2mnz]] – hLSD 5B zinc finger domain 1 + histone 3 peptide - NMR<br /> | ||
**[[4fwf]] – hLSD1 + histone 3.1 peptide<br /> | **[[4fwf]] – hLSD1 + histone 3.1 peptide<br /> | ||
| - | **[[4gu0]] – hLSD2 + histone 3.3 peptide<br /> | ||
| - | **[[4gur]], [[4gus]], [[4hsu]] – hLSD2 + histone 3.3 peptide + oxidoreductase<br /> | ||
*LSD1 complex with CoREST | *LSD1 complex with CoREST | ||
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**[[2x0l]] - hLSD1 residues 123-852 + CoREST SANT1 and SANT2 domains + histone H3 residues 1-16<br /> | **[[2x0l]] - hLSD1 residues 123-852 + CoREST SANT1 and SANT2 domains + histone H3 residues 1-16<br /> | ||
**[[2xaf]], [[2xag]], [[2xah]], [[2xaj]], [[2xaq]], [[2xas]] - hLSD1 residues 123-852 + CoREST SANT1 and SANT2 domains + tranylcypromine derivative<br /> | **[[2xaf]], [[2xag]], [[2xah]], [[2xaj]], [[2xaq]], [[2xas]] - hLSD1 residues 123-852 + CoREST SANT1 and SANT2 domains + tranylcypromine derivative<br /> | ||
| - | **[[2y48]] - | + | **[[2y48]] - hLSD1 residues 123-852 + CoREST SANT1 and SANT2 domains + zinc finger protein SNAIL N terminal<br /> |
| - | **[[3zms]], [[3zmt]], [[3zmu]], [[3zmv]], [[3zmz]], [[3zn0]], [[3zn1]] - | + | **[[3zms]], [[3zmt]], [[3zmu]], [[3zmv]], [[3zmz]], [[3zn0]], [[3zn1]] - hLSD1 residues 123-852 + CoREST SANT1 and SANT2 domains + zinc finger protein IA-1 peptide <br /> |
| - | **[[4bay]] - | + | **[[4bay]] - hLSD1 residues 192-876 + CoREST residues 308-440 <br /> |
| - | **[[4kum]] - | + | **[[4kum]] - hLSD1 SWIRM + FAD domains + CoREST residues 289-485 <br /> |
| - | **[[4czz]] - | + | **[[4czz]] - hLSD1 + CoREST <br /> |
| - | **[[4uv8]], [[4uv9]], [[4uva]], [[4uvb]], [[4ubc]] - | + | **[[4uv8]], [[4uv9]], [[4uva]], [[4uvb]], [[4ubc]] - hLSD1 + CoREST + irreversible inhibitor<br /> |
| - | **[[4uxn]] - | + | **[[4uxn]] - hLSD1 + CoREST + pyrrolydine inhibitor<br /> |
| + | *lysine-specific histone demethylase 2 | ||
| + | |||
| + | **[[4gu1]] – hLSD2<br /> | ||
| + | **[[4gur]], [[4gus]], [[4hsu]] – hLSD2 + NPAC + histone 3.3 peptide <br /> | ||
| + | **[[4gut]] – hLSD2 + NPAC <br /> | ||
| + | **[[4guu]] – hLSD2 + NPAC + tranylcypromine <br /> | ||
| + | **[[4gu0]] – hLSD2 + histone 3.3 peptide <br /> | ||
| + | |||
| + | *lysine-specific histone demethylase 5B | ||
| + | |||
| + | **[[2ma5]] – hLSD5B zinc finger domain 3 - NMR<br /> | ||
| + | **[[2mny]] – hLSD5B zinc finger domain 1 - NMR<br /> | ||
| + | **[[2mnz]] – hLSD5B zinc finger domain 1 + histone 3 peptide - NMR<br /> | ||
}} | }} | ||
== References == | == References == | ||
<references/> | <references/> | ||
[[Category:Topic Page]] | [[Category:Topic Page]] | ||
Revision as of 10:21, 13 April 2016
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].
3D structures of lysine-specific histone demethylase 1
Updated on 13-April-2016
References
- ↑ 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
- ↑ 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
- ↑ 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
- ↑ 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
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Michal Harel, Alexander Berchansky, Joel L. Sussman, Jaime Prilusky
