5icn

From Proteopedia

(Difference between revisions)

Revision as of 20:36, 24 January 2018

HDAC1:MTA1 in complex with inositol-6-phosphate and a novel peptide inhibitor based on histone H4

Structural highlights

5icn is a 3 chain structure with sequence from Human and Synthetic construct sequences. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, ,
NonStd Res:
Gene:	MTA1 (HUMAN), HDAC1, RPD3L1 (HUMAN), HDAC1 (HUMAN)
Activity:	Histone deacetylase, with EC number 3.5.1.98
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[MTA1_HUMAN] May be involved in the regulation of gene expression by covalent modification of histone proteins. Isoform Long is a corepressor of estrogen receptor (ER). Isoform Short binds to ER and sequesters it in the cytoplasm and enhances non-genomic responses of ER. [HDAC1_HUMAN] Responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4). Histone deacetylation gives a tag for epigenetic repression and plays an important role in transcriptional regulation, cell cycle progression and developmental events. Histone deacetylases act via the formation of large multiprotein complexes. Deacetylates SP proteins, SP1 and SP3, and regulates their function. Component of the BRG1-RB1-HDAC1 complex, which negatively regulates the CREST-mediated transcription in resting neurons. Upon calcium stimulation, HDAC1 is released from the complex and CREBBP is recruited, which facilitates transcriptional activation. Deacetylates TSHZ3 and regulates its transcriptional repressor activity. Deacetylates 'Lys-310' in RELA and thereby inhibits the transcriptional activity of NF-kappa-B. Component a RCOR/GFI/KDM1A/HDAC complex that suppresses, via histone deacetylase (HDAC) recruitment, a number of genes implicated in multilineage blood cell development.^[1] ^[2] ^[3] ^[4] ^[5] ^[6]

Publication Abstract from PubMed

Histone deacetylases (HDACs) 1, 2 and 3 form the catalytic subunit of several large transcriptional repression complexes. Unexpectedly, the enzymatic activity of HDACs in these complexes has been shown to be regulated by inositol phosphates, which bind in a pocket sandwiched between the HDAC and co-repressor proteins. However, the actual mechanism of activation remains poorly understood. Here we have elucidated the stereochemical requirements for binding and activation by inositol phosphates, demonstrating that activation requires three adjacent phosphate groups and that other positions on the inositol ring can tolerate bulky substituents. We also demonstrate that there is allosteric communication between the inositol-binding site and the active site. The crystal structure of the HDAC1:MTA1 complex bound to a novel peptide-based inhibitor and to inositol hexaphosphate suggests a molecular basis of substrate recognition, and an entropically driven allosteric mechanism of activation.

Insights into the activation mechanism of class I HDAC complexes by inositol phosphates.,Watson PJ, Millard CJ, Riley AM, Robertson NS, Wright LC, Godage HY, Cowley SM, Jamieson AG, Potter BV, Schwabe JW Nat Commun. 2016 Apr 25;7:11262. doi: 10.1038/ncomms11262. PMID:27109927^[7]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Ammanamanchi S, Freeman JW, Brattain MG. Acetylated sp3 is a transcriptional activator. J Biol Chem. 2003 Sep 12;278(37):35775-80. Epub 2003 Jun 30. PMID:12837748 doi:http://dx.doi.org/10.1074/jbc.M305961200
↑ Hung JJ, Wang YT, Chang WC. Sp1 deacetylation induced by phorbol ester recruits p300 to activate 12(S)-lipoxygenase gene transcription. Mol Cell Biol. 2006 Mar;26(5):1770-85. PMID:16478997 doi:http://dx.doi.org/10.1128/MCB.26.5.1770-1785.2006
↑ Liu Y, Smith PW, Jones DR. Breast cancer metastasis suppressor 1 functions as a corepressor by enhancing histone deacetylase 1-mediated deacetylation of RelA/p65 and promoting apoptosis. Mol Cell Biol. 2006 Dec;26(23):8683-96. Epub 2006 Sep 25. PMID:17000776 doi:10.1128/MCB.00940-06
↑ Wang C, Rauscher FJ 3rd, Cress WD, Chen J. Regulation of E2F1 function by the nuclear corepressor KAP1. J Biol Chem. 2007 Oct 12;282(41):29902-9. Epub 2007 Aug 17. PMID:17704056 doi:10.1074/jbc.M704757200
↑ Qiu Z, Ghosh A. A calcium-dependent switch in a CREST-BRG1 complex regulates activity-dependent gene expression. Neuron. 2008 Dec 10;60(5):775-87. doi: 10.1016/j.neuron.2008.09.040. PMID:19081374 doi:http://dx.doi.org/10.1016/j.neuron.2008.09.040
↑ Kajiwara Y, Akram A, Katsel P, Haroutunian V, Schmeidler J, Beecham G, Haines JL, Pericak-Vance MA, Buxbaum JD. FE65 binds Teashirt, inhibiting expression of the primate-specific caspase-4. PLoS One. 2009;4(4):e5071. doi: 10.1371/journal.pone.0005071. Epub 2009 Apr 3. PMID:19343227 doi:10.1371/journal.pone.0005071
↑ Watson PJ, Millard CJ, Riley AM, Robertson NS, Wright LC, Godage HY, Cowley SM, Jamieson AG, Potter BV, Schwabe JW. Insights into the activation mechanism of class I HDAC complexes by inositol phosphates. Nat Commun. 2016 Apr 25;7:11262. doi: 10.1038/ncomms11262. PMID:27109927 doi:http://dx.doi.org/10.1038/ncomms11262

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5icn"

@@ Line 3: / Line 3: @@
 <StructureSection load='5icn' size='340' side='right' caption='[[5icn]], [[Resolution|resolution]] 3.30&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5icn]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5ICN OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5ICN FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5icn]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human] and [http://en.wikipedia.org/wiki/Synthetic_construct_sequences Synthetic construct sequences]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5ICN OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5ICN FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=I6P:INOSITOL+1,2,3,4,5,6-HEXAKISPHOSPHATE'>I6P</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
 <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=6A0:(2S)-2-AMINO-8-(HYDROXYAMINO)-8-OXOOCTANOIC+ACID'>6A0</scene></td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MTA1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), HDAC1, RPD3L1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), HDAC1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
 <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Histone_deacetylase Histone deacetylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.1.98 3.5.1.98] </span></td></tr>
 <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=5icn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5icn OCA], [http://pdbe.org/5icn PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5icn RCSB], [http://www.ebi.ac.uk/pdbsum/5icn PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5icn ProSAT]</span></td></tr>
@@ Line 20: / Line 21: @@
 </div>
 <div class="pdbe-citations 5icn" style="background-color:#fffaf0;"></div>
-==See Also==
-*[[Histone deacetylase|Histone deacetylase]]
 == References ==
 <references/>
@@ Line 28: / Line 26: @@
 </StructureSection>
 [[Category: Histone deacetylase]]
+[[Category: Human]]
+[[Category: Synthetic construct sequences]]
 [[Category: Jameson, A G]]
 [[Category: Millard, C J]]

5icn

From Proteopedia

Revision as of 20:36, 24 January 2018

HDAC1:MTA1 in complex with inositol-6-phosphate and a novel peptide inhibitor based on histone H4

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox