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| | <StructureSection load='4bkx' size='340' side='right'caption='[[4bkx]], [[Resolution|resolution]] 3.00Å' scene=''> | | <StructureSection load='4bkx' size='340' side='right'caption='[[4bkx]], [[Resolution|resolution]] 3.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4bkx]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4BKX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4BKX FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4bkx]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4BKX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4BKX FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3Å</td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Histone_deacetylase Histone deacetylase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.1.98 3.5.1.98] </span></td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> |
| | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4bkx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4bkx OCA], [https://pdbe.org/4bkx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4bkx RCSB], [https://www.ebi.ac.uk/pdbsum/4bkx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4bkx ProSAT]</span></td></tr> | | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4bkx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4bkx OCA], [https://pdbe.org/4bkx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4bkx RCSB], [https://www.ebi.ac.uk/pdbsum/4bkx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4bkx ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/MTA1_HUMAN 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. [[https://www.uniprot.org/uniprot/HDAC1_HUMAN 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.<ref>PMID:12837748</ref> <ref>PMID:16478997</ref> <ref>PMID:17000776</ref> <ref>PMID:17704056</ref> <ref>PMID:19081374</ref> <ref>PMID:19343227</ref>
| + | [https://www.uniprot.org/uniprot/MTA1_HUMAN 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. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Histone deacetylase]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Human]]
| + | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Celardo, I]] | + | [[Category: Celardo I]] |
| - | [[Category: Cowley, S M]] | + | [[Category: Cowley SM]] |
| - | [[Category: Fairall, L]] | + | [[Category: Fairall L]] |
| - | [[Category: Gordiyenko, Y]] | + | [[Category: Gordiyenko Y]] |
| - | [[Category: Millard, C J]] | + | [[Category: Millard CJ]] |
| - | [[Category: Robinson, C V]] | + | [[Category: Robinson CV]] |
| - | [[Category: Schwabe, J W.R]] | + | [[Category: Schwabe JWR]] |
| - | [[Category: Watson, P J]] | + | [[Category: Watson PJ]] |
| - | [[Category: Elm2-sant domain]]
| + | |
| - | [[Category: Hdac]]
| + | |
| - | [[Category: Hdac1]]
| + | |
| - | [[Category: Inositol phosphate signalling]]
| + | |
| - | [[Category: Mta1]]
| + | |
| - | [[Category: Transcription]]
| + | |
| Structural highlights
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.
Publication Abstract from PubMed
Class I histone deacetylases (HDAC1, HDAC2, and HDAC3) are recruited by cognate corepressor proteins into specific transcriptional repression complexes that target HDAC activity to chromatin resulting in chromatin condensation and transcriptional silencing. We previously reported the structure of HDAC3 in complex with the SMRT corepressor. This structure revealed the presence of inositol-tetraphosphate [Ins(1,4,5,6)P4] at the interface of the two proteins. It was previously unclear whether the role of Ins(1,4,5,6)P4 is to act as a structural cofactor or a regulator of HDAC3 activity. Here we report the structure of HDAC1 in complex with MTA1 from the NuRD complex. The ELM2-SANT domains from MTA1 wrap completely around HDAC1 occupying both sides of the active site such that the adjacent BAH domain is ideally positioned to recruit nucleosomes to the active site of the enzyme. Functional assays of both the HDAC1 and HDAC3 complexes reveal that Ins(1,4,5,6)P4 is a bona fide conserved regulator of class I HDAC complexes.
Class I HDACs Share a Common Mechanism of Regulation by Inositol Phosphates.,Millard CJ, Watson PJ, Celardo I, Gordiyenko Y, Cowley SM, Robinson CV, Fairall L, Schwabe JW Mol Cell. 2013 Jun 19. pii: S1097-2765(13)00407-3. doi:, 10.1016/j.molcel.2013.05.020. PMID:23791785[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Millard CJ, Watson PJ, Celardo I, Gordiyenko Y, Cowley SM, Robinson CV, Fairall L, Schwabe JW. Class I HDACs Share a Common Mechanism of Regulation by Inositol Phosphates. Mol Cell. 2013 Jun 19. pii: S1097-2765(13)00407-3. doi:, 10.1016/j.molcel.2013.05.020. PMID:23791785 doi:10.1016/j.molcel.2013.05.020
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