6g0s

From Proteopedia

(Difference between revisions)

Revision as of 20:31, 2 December 2018

Crystal Structure of the first bromodomain of human BRD4 in complex with an acetylated SIRT7 peptide (K272ac/K275ac)

Structural highlights

6g0s is a 3 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
NonStd Res:
Gene:	BRD4, HUNK1 (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[BRD4_HUMAN] Note=A chromosomal aberration involving BRD4 is found in a rare, aggressive, and lethal carcinoma arising in midline organs of young people. Translocation t(15;19)(q14;p13) with NUT which produces a BRD4-NUT fusion protein.^[1] ^[2]

Function

[BRD4_HUMAN] Plays a role in a process governing chromosomal dynamics during mitosis (By similarity). [SIR7_HUMAN] NAD-dependent protein deacetylase that specifically mediates deacetylation of histone H3 at 'Lys-18' (H3K18Ac). In contrast to other histone deacetylases, displays selectivity for a single histone mark, H3K18Ac, directly linked to control of gene expression. H3K18Ac is mainly present around the transcription start site of genes and has been linked to activation of nuclear hormone receptors. SIRT7 thereby acts as a transcription repressor. Moreover, H3K18 hypoacetylation has been reported as a marker of malignancy in various cancers and seems to maintain the transformed phenotype of cancer cells. These data suggest that SIRT7 may play a key role in oncogenic transformation by suppresses expression of tumor suppressor genes by locus-specific deacetylation of H3K18Ac at promoter regions. Also required to restore the transcription of ribosomal RNA (rRNA) at the exit from mitosis: promotes the association of RNA polymerase I with the rDNA promoter region and coding region. Stimulates transcription activity of the RNA polymerase I complex. May also deacetylate p53/TP53 and promotes cell survival, however such data need additional confirmation.^[3] ^[4] ^[5]

References

↑ French CA, Miyoshi I, Kubonishi I, Grier HE, Perez-Atayde AR, Fletcher JA. BRD4-NUT fusion oncogene: a novel mechanism in aggressive carcinoma. Cancer Res. 2003 Jan 15;63(2):304-7. PMID:12543779
↑ French CA, Miyoshi I, Aster JC, Kubonishi I, Kroll TG, Dal Cin P, Vargas SO, Perez-Atayde AR, Fletcher JA. BRD4 bromodomain gene rearrangement in aggressive carcinoma with translocation t(15;19). Am J Pathol. 2001 Dec;159(6):1987-92. PMID:11733348 doi:10.1016/S0002-9440(10)63049-0
↑ Ford E, Voit R, Liszt G, Magin C, Grummt I, Guarente L. Mammalian Sir2 homolog SIRT7 is an activator of RNA polymerase I transcription. Genes Dev. 2006 May 1;20(9):1075-80. doi: 10.1101/gad.1399706. Epub 2006 Apr 17. PMID:16618798 doi:http://dx.doi.org/10.1101/gad.1399706
↑ Grob A, Roussel P, Wright JE, McStay B, Hernandez-Verdun D, Sirri V. Involvement of SIRT7 in resumption of rDNA transcription at the exit from mitosis. J Cell Sci. 2009 Feb 15;122(Pt 4):489-98. doi: 10.1242/jcs.042382. Epub 2009 Jan , 27. PMID:19174463 doi:http://dx.doi.org/10.1242/jcs.042382
↑ Barber MF, Michishita-Kioi E, Xi Y, Tasselli L, Kioi M, Moqtaderi Z, Tennen RI, Paredes S, Young NL, Chen K, Struhl K, Garcia BA, Gozani O, Li W, Chua KF. SIRT7 links H3K18 deacetylation to maintenance of oncogenic transformation. Nature. 2012 Jul 5;487(7405):114-8. doi: 10.1038/nature11043. PMID:22722849 doi:http://dx.doi.org/10.1038/nature11043

1 Structural highlights
2 Disease
3 Function
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6g0s"

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 6g0s is ON HOLD
+==Crystal Structure of the first bromodomain of human BRD4 in complex with an acetylated SIRT7 peptide (K272ac/K275ac)==
+<StructureSection load='6g0s' size='340' side='right' caption='[[6g0s]], [[Resolution|resolution]] 1.48&Aring;' scene=''>
-Authors: Filippakopoulos, P., Picaud, S., Krojer, T., von Delft, F., Arrowsmith, C.H., Edwards, A.M., Bountra, C.
+== Structural highlights ==
+<table><tr><td colspan='2'>[[6g0s]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6G0S OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6G0S FirstGlance]. <br>
-Description: Crystal Structure of the first bromodomain of human BRD4 in complex with an acetylated SIRT7 peptide (K272ac/K275ac)
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene></td></tr>
-[[Category: Unreleased Structures]]
+<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=ALY:N(6)-ACETYLLYSINE'>ALY</scene></td></tr>
-[[Category: Arrowsmith, C.H]]
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">BRD4, HUNK1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
-[[Category: Von Delft, F]]
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6g0s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6g0s OCA], [http://pdbe.org/6g0s PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6g0s RCSB], [http://www.ebi.ac.uk/pdbsum/6g0s PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6g0s ProSAT]</span></td></tr>
-[[Category: Picaud, S]]
+</table>
+== Disease ==
+[[http://www.uniprot.org/uniprot/BRD4_HUMAN BRD4_HUMAN]] Note=A chromosomal aberration involving BRD4 is found in a rare, aggressive, and lethal carcinoma arising in midline organs of young people. Translocation t(15;19)(q14;p13) with NUT which produces a BRD4-NUT fusion protein.<ref>PMID:12543779</ref> <ref>PMID:11733348</ref>
+== Function ==
+[[http://www.uniprot.org/uniprot/BRD4_HUMAN BRD4_HUMAN]] Plays a role in a process governing chromosomal dynamics during mitosis (By similarity). [[http://www.uniprot.org/uniprot/SIR7_HUMAN SIR7_HUMAN]] NAD-dependent protein deacetylase that specifically mediates deacetylation of histone H3 at 'Lys-18' (H3K18Ac). In contrast to other histone deacetylases, displays selectivity for a single histone mark, H3K18Ac, directly linked to control of gene expression. H3K18Ac is mainly present around the transcription start site of genes and has been linked to activation of nuclear hormone receptors. SIRT7 thereby acts as a transcription repressor. Moreover, H3K18 hypoacetylation has been reported as a marker of malignancy in various cancers and seems to maintain the transformed phenotype of cancer cells. These data suggest that SIRT7 may play a key role in oncogenic transformation by suppresses expression of tumor suppressor genes by locus-specific deacetylation of H3K18Ac at promoter regions. Also required to restore the transcription of ribosomal RNA (rRNA) at the exit from mitosis: promotes the association of RNA polymerase I with the rDNA promoter region and coding region. Stimulates transcription activity of the RNA polymerase I complex. May also deacetylate p53/TP53 and promotes cell survival, however such data need additional confirmation.<ref>PMID:16618798</ref> <ref>PMID:19174463</ref> <ref>PMID:22722849</ref>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Human]]
+[[Category: Arrowsmith, C H]]
+[[Category: Bountra, C]]
+[[Category: Delft, F von]]
+[[Category: Edwards, A M]]
 [[Category: Filippakopoulos, P]]
-[[Category: Edwards, A.M]]
 [[Category: Krojer, T]]
-[[Category: Bountra, C]]
+[[Category: Picaud, S]]
+[[Category: Bromodomain]]
+[[Category: Complex]]
+[[Category: Transcription]]

6g0s

From Proteopedia

Revision as of 20:31, 2 December 2018

Crystal Structure of the first bromodomain of human BRD4 in complex with an acetylated SIRT7 peptide (K272ac/K275ac)

Structural highlights

Disease

Function

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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