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Histone deacetylase

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* '''HDAC class I''' are homologous to yeast Rpd3.<br />
* '''HDAC class I''' are homologous to yeast Rpd3.<br />
* '''HDAC class II''' are homologous to yeast HdaI.<br />
* '''HDAC class II''' are homologous to yeast HdaI.<br />
-
* '''HDAC class III''' called '''sirtuin''' - (Silent Information Regulator) (SIRT) are NAD-dependent HDAC <ref>PMID:18249170</ref>.<br />
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* '''HDAC class III''' called '''sirtuin''' - (Silent Information Regulator) (SIRT) are NAD-dependent HDAC. This protein is bifunctional and can act as a deacylase or as mono-ADP-acetyltransferase. <ref>PMID:18249170</ref>.<br />
 +
 
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For HDAC8 see - [[Histone deacetylase 8 (HDAC8)]].<br />
For additional details see<br />
For additional details see<br />
* [[Understanding of the Recruitment of HDACs by MEF2, Based on Their Structure]]<br />
* [[Understanding of the Recruitment of HDACs by MEF2, Based on Their Structure]]<br />
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== Relevance ==
== Relevance ==
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HDAC inhibitors are used in cancer therapy<ref>PMID:11902574</ref>. Sirtuins play a role in cancer, metabolic activity and neurodegenerative diseases<ref>PMID:17456799</ref>. HDAC inhibitor SAHA or Vorinostat is used in the treatment of cutaneous T cell lymphoma<ref>PMID:17962618</ref>.
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HDAC inhibitors are used in cancer therapy<ref>PMID:11902574</ref>. Sirtuins play a role in cancer, metabolic activity and neurodegenerative diseases<ref>PMID:17456799</ref>. HDAC inhibitor SAHA or [[Zolinza (Vorinostat)]] is used in the treatment of cutaneous T cell lymphoma<ref>PMID:17962618</ref>.
== Structural highlights ==
== Structural highlights ==
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The biological assembly of Human sirtuin-3 is <scene name='48/483191/Cv/2'>homodimer</scene>. The <scene name='48/483191/Cv/4'>acetylated lysine of the peptide is inserted in an extended conformation</scene> between the 2 domains of SIRT3 - a large Rossman fold, NAD-binding domain and a small Zn-binding one)<ref>PMID:19535340</ref>.<br />. Water molecule shown as red sphere.
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The biological assembly of Human sirtuin-3 is <scene name='48/483191/Cv/5'>homodimer</scene>. The <scene name='48/483191/Cv/6'>acetylated lysine of the peptide is inserted in an extended conformation</scene> between the 2 domains of SIRT3 - a large Rossman fold, NAD-binding domain and a small Zn-binding one)<ref>PMID:19535340</ref>. Water molecule shown as red sphere.
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</StructureSection>
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== 3D Structures of histone deacetylase ==
== 3D Structures of histone deacetylase ==
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[[Histone deacetylase 3D structures]]
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Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}
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</StructureSection>
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{{#tree:id=OrganizedByTopic|openlevels=0|
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*'''HDAC class I'''
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*HDAC1
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-
 
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**[[4bkx]] – hHDAC1 + MTA1 – human<br />
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-
**[[3hgq]], [[3hgt]] – hHDAC1 subunit 3<br />
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**[[5icn]] – hHDAC1 + MTA1 + peptide<br />
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**[[5j8j]] – yHDAC1 residues 457-698 – yeast<br />
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-
 
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*HDAC2
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-
 
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**[[3max]] – hHDAC2 + amide derivative <br />
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-
**[[4lxz]] – hHDAC2 core domain + SAHA<br />
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-
**[[4ly1]], [[5iwg]], [[5ix0]] – hHDAC2 core domain + inhibitor<br />
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-
 
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*HDAC3
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-
 
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**[[4a69]] – hHDAC3 + nuclear receptor corepressor 2 + inositol tetraphosphate
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-
 
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*HDAC8
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-
 
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-
**[[3ew8]], [[3ezp]], [[3ezt]], [[3f06]] – hHDAC8 (mutant)<br />
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-
**[[3sff]], [[3sfh]] – hHDAC8 + inhibitor<br />
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-
**[[1t64]], [[3f0r]], [[5ths]] – hHDAC8 + trichostatin A <br />
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-
**[[5tht]], [[5thu]], [[5thv]], [[5dc5]], [[5d1b]] - hHDAC8 (mutant) + amide derivative<br />
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-
**[[1t67]], [[1w22]], [[1vkg]], [[3f07]] - hHDAC8 + amide derivative<br />
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-
**[[1t69]] - hHDAC8 + SAHA<br />
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-
**[[4qa0]] - hHDAC8 (mutant) + SAHA<br />
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-
**[[5fcw]], [[5fue]] - hHDAC8 + hydroxamate<br />
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-
**[[4qa1]], [[4qa2]], [[4qa3]], [[4qa4]] - hHDAC8 (mutant) + inhibitor<br />
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-
**[[2v5w]] – hHDAC8 + tripeptide substrate<br />
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-
**[[4qa5]], [[4qa6]], [[4qa7]], [[3ewf]], [[5dc8]], [[5dc7]], [[5dc6]], [[5d1d]], [[5d1c]] - hHDAC8 (mutant) + tetrapeptide substrate<br />
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**[[3rqd]] - hHDAC8 + largazole<br />
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**[[4rn0]], [[4rn1]], [[4rn2]] - hHDAC8 (mutant) + largazole analog<br />
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**[[5bwz]] - hHDAC8 (mutant) + droxinostat<br />
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**[[3mz3]] - hHDAC8 (Co) + amide derivative<br />
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**[[3mz7]] - hHDAC8 (Co) (mutant) + amide derivative<br />
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**[[3mz4]] - hHDAC8 (Mn) (mutant) + amide derivative<br />
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**[[3mz6]] - hHDAC8 (Fe) (mutant) + amide derivative<br />
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**[[2v5x]] - hHDAC8 (mutant) + octanediamide derivative<br />
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**[[4bz5]] – SmHDAC8 – ''Schistosoma mansoni''<br />
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**[[4bz7]], [[4bz8]], [[4bz9]], [[4cqf]] – SmHDAC8 + inhibitor<br />
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**[[4bz6]] – SmHDAC8 + SAHA<br />
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*'''HDAC class IIA'''
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*HDAC4
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**[[2h8n]] – hHDAC4 N terminal <br />
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**[[2o94]] - hHDAC4 N terminal (mutant)<br />
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**[[2vqw]] - hHDAC4 catalytic domain (mutant)<br />
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**[[2vqj]], [[2vqm]], [[4cbt]], [[5a2s]] – hHDAC4 catalytic domain + inhibitor<br />
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**[[2vqo]], [[2vqq]], [[2vqv]], [[4cby]] – hHDAC4 catalytic domain (mutant) + inhibitor
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*HDAC7
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**[[3c0y]] – hHDAC7 catalytic domain<br />
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**[[3c0z]] - hHDAC7 catalytic domain + octanedioic acid hydroxyamide phenylamide<br />
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**[[3c10]] - hHDAC7 catalytic domain + trichostatin A<br />
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**[[3znr]], [[3zns]] - hHDAC7 catalytic domain + inhibitor<br />
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*HDAC9
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**[[1tqe]] – mHDAC9 + myocyte-specific enhancer factor + DNA – mouse
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*HDAC
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**[[4a6q]], [[4a90]] - hHDAC subunit SAP18 <br />
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**[[2hde]] – hHDAC subunit SAP18 (mutant) – NMR<br />
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**[[4a8x]] - hHDAC subunit SAP18 + RNA-binding protein + hook-like<br />
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**[[2kdp]] – hHDAC subunit SAP30 – NMR<br />
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**[[2ld7]] – hHDAC subunit SAP30 +SIN3A PAH 3 domain – NMR<br />
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**[[5ikk]] – HDAC CLR3 – fission yeast<br />
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*'''HDAC class IIB'''
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*HDAC6
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**[[3c5k]] – hHDAC6 zinc finger domain<br />
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**[[3gv4]] - hHDAC6 zinc finger domain + ubiquitin peptide<br />
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**[[3phd]] - hHDAC6 + polyubiquitin<br />
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**[[5kh3]], [[5kh7]], [[5kh9]], [[5b8d]] – hHDAC6 zinc finger + inhibitor<br />
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*'''HDAC class III'''
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*SIRT1
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**[[4ig9]] – hSIRT1 + Zn<br />
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**[[4i5i]] – hSIRT1 + NAD + indole + Zn<br />
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**[[4if6]], [[4kxq]] – hSIRT1 + ADP-ribose + Zn<br />
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**[[5btr]] – hSIRT1 + acetyl lysine peptide + resveratol + Zn<br />
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**[[4zzh]] – hSIRT1 + activator + Zn<br />
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**[[4zzi]] – hSIRT1 + activator + inhibitor + Zn<br />
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**[[4zzj]] – hSIRT1 + acetyl lysine peptide + activator + Zn<br />
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*SIRT2
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**[[2hjh]] – ySIRT2 + pseudosubstrate + nicotinamide + Zn <br />
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**[[4iao]] – ySIRT2 + SIRT4 + ADP-ribose + Zn<br />
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**[[1j8f]], [[3zgo]] – hSIRT2 + Zn<br />
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**[[3zgv]], [[5d7o]] – hSIRT2+ ADP ribose + Zn<br />
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**[[4y6q]] – hSIRT2+ ADP ribose derivative + Zn<br />
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**[[4l3o]], [[4y6l]], [[4y6o]] – hSIRT2 + acetyl lysine peptide + Zn<br />
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**[[4x3o]], [[4x3p]] – hSIRT2 + myristoyl peptide + Zn<br />
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**[[4rmg]], [[5dy4]], [[5dy5]] – hSIRT2 + inhibitor + Zn<br />
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**[[5d7p]], [[5d7q]] – hSIRT2 + inhibitor + ADP-ribose + Zn<br />
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**[[4rmh]], [[4rmi]] – hSIRT2 + acetyl lysine peptide + inhibitor + Zn<br />
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**[[4r8m]] – hSIRT2 + peptide + tridecanethial + Zn<br />
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**[[4rmj]] – hSIRT2 + ADP-ribose + nicotinamide + Zn <br />
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*SIRT3
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**[[5d7n]] – hSIRT3 + Zn<br />
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**[[3gls]] – hSIRT3 (mutant) + Zn<br />
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**[[3glu]] – hSIRT3 + peptide + Zn<br />
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**[[3glr]], [[3glt]], [[4fvt]], [[4bve]], [[4v1c]] – hSIRT3 + acetyl lysine peptide + Zn<br />
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**[[4hd8]] – hSIRT3 + acetyl lysine peptide + piceatannol + Zn<br />
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**[[4fz3]] – hSIRT3 + acetyl lysine peptide + coumarine derivative + Zn<br />
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**[[4c78]], [[4c7b]] – hSIRT3 + acetyl lysine peptide + resveratol derivative + Zn<br />
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-
**[[4jsr]], [[4jt8]], [[4jt9]], [[4o8z]] – hSIRT3 + inhibitor + Zn<br />
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-
**[[4gbn5]] – hSIRT3 + inhibitor + carba-NAD + Zn<br/ >
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**[[4bv3]] – hSIRT3 + inhibitor + NAD + ADP-ribose + Zn<br />
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**[[4bvb]], [[4bvh]] – hSIRT3 + inhibitor + ADP-ribose + Zn<br />
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**[[4bvf]], [[4bvg]] – hSIRT3 + acetyl lysine peptide + inhibitor + Zn<br />
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*SIRT5
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**[[2b4y]], [[4bn4]] – hSIRT5 + ADP-ribose + Zn<br />
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**[[2nyr]] – hSIRT5 + suramine + Zn<br />
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-
 
+
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**[[3rig]], [[3riy]], [[4f4u]] – hSIRT5 + acetyl lysine peptide + Zn<br />
+
-
**[[4gic]] – hSIRT5 + acetyl lysine peptide + carba-NAD + Zn<br/ >
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-
**[[4f56]] – hSIRT5 + peptide + intermediate + Zn<br />
+
-
**[[4hda]] – hSIRT5 + acetyl lysine peptide + resveratrol + Zn<br />
+
-
**[[4utn]], [[4utr]], [[4utv]], [[4utx]], [[4utz]], [[4uu7]], [[4uu8]], [[4uua]], [[4uub]] – zeSIRT5 + acetyl lysine peptide + inhibitor + Zn - zebrafish<br />
+
-
 
+
-
 
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*SIRT6
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-
 
+
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**[[3k35]] – hSIRT6 + ADP-ribose + Zn<br />
+
-
**[[3pki]], [[3pkj]] – hSIRT6 (mutant) + ADP-ribose derivative + Zn<br />
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**[[3zg6]] – hSIRT6 + acetyl lysine peptide + ADP-ribose + Zn<br />
+
-
}}
 
== References ==
== References ==
<references/>
<references/>
[[Category:Topic Page]]
[[Category:Topic Page]]

Current revision

Human sirtuin-3 complex with peptide containing acetylated lysine, sulfate, carbonate, glycerol and Zn+2 ion (PDB entry 3glr)

Drag the structure with the mouse to rotate

References

  1. ↑ Joshi P, Greco TM, Guise AJ, Luo Y, Yu F, Nesvizhskii AI, Cristea IM. The functional interactome landscape of the human histone deacetylase family. Mol Syst Biol. 2013;9:672. doi: 10.1038/msb.2013.26. PMID:23752268 doi:http://dx.doi.org/10.1038/msb.2013.26
  2. ↑ Schwer B, Verdin E. Conserved metabolic regulatory functions of sirtuins. Cell Metab. 2008 Feb;7(2):104-12. doi: 10.1016/j.cmet.2007.11.006. PMID:18249170 doi:http://dx.doi.org/10.1016/j.cmet.2007.11.006
  3. ↑ Marks P, Rifkind RA, Richon VM, Breslow R, Miller T, Kelly WK. Histone deacetylases and cancer: causes and therapies. Nat Rev Cancer. 2001 Dec;1(3):194-202. PMID:11902574 doi:http://dx.doi.org/10.1038/35106079
  4. ↑ Yamamoto H, Schoonjans K, Auwerx J. Sirtuin functions in health and disease. Mol Endocrinol. 2007 Aug;21(8):1745-55. Epub 2007 Apr 24. PMID:17456799 doi:http://dx.doi.org/10.1210/me.2007-0079
  5. ↑ Mann BS, Johnson JR, Cohen MH, Justice R, Pazdur R. FDA approval summary: vorinostat for treatment of advanced primary cutaneous T-cell lymphoma. Oncologist. 2007 Oct;12(10):1247-52. PMID:17962618 doi:http://dx.doi.org/10.1634/theoncologist.12-10-1247
  6. ↑ Jin L, Wei W, Jiang Y, Peng H, Cai J, Mao C, Dai H, Choy W, Bemis JE, Jirousek MR, Milne JC, Westphal CH, Perni RB. Crystal structures of human SIRT3 displaying substrate-induced conformational changes. J Biol Chem. 2009 Sep 4;284(36):24394-405. Epub 2009 Jun 16. PMID:19535340 doi:10.1074/jbc.M109.014928

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