3toa: Difference between revisions
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[[ | ==Human MOF crystal structure with active site lysine partially acetylated== | ||
<StructureSection load='3toa' size='340' side='right' caption='[[3toa]], [[Resolution|resolution]] 3.00Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[3toa]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3TOA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3TOA FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</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=ALY:N(6)-ACETYLLYSINE'>ALY</scene></td></tr> | |||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3to6|3to6]], [[3to7|3to7]], [[3to9|3to9]], [[3tob|3tob]]</td></tr> | |||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MYST1, MOF, PP7073 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr> | |||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Histone_acetyltransferase Histone acetyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.1.48 2.3.1.48] </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=3toa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3toa OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3toa RCSB], [http://www.ebi.ac.uk/pdbsum/3toa PDBsum]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The MYST protein lysine acetyltransferases are evolutionarily conserved throughout eukaryotes and acetylate proteins to regulate diverse biological processes including gene regulation, DNA repair, cell-cycle regulation, stem cell homeostasis and development. Here, we demonstrate that MYST protein acetyltransferase activity requires active site lysine autoacetylation. The X-ray crystal structures of yeast Esa1 (yEsa1/KAT5) bound to a bisubstrate H4K16CoA inhibitor and human MOF (hMOF/KAT8/MYST1) reveal that they are autoacetylated at a strictly conserved lysine residue in MYST proteins (yEsa1-K262 and hMOF-K274) in the enzyme active site. The structure of hMOF also shows partial occupancy of K274 in the unacetylated form, revealing that the side chain reorients to a position that engages the catalytic glutamate residue and would block cognate protein substrate binding. Consistent with the structural findings, we present mass spectrometry data and biochemical experiments to demonstrate that this lysine autoacetylation on yEsa1, hMOF and its yeast orthologue, ySas2 (KAT8) occurs in solution and is required for acetylation and protein substrate binding in vitro. We also show that this autoacetylation occurs in vivo and is required for the cellular functions of these MYST proteins. These findings provide an avenue for the autoposttranslational regulation of MYST proteins that is distinct from other acetyltransferases but draws similarities to the phosphoregulation of protein kinases. | |||
MYST protein acetyltransferase activity requires active site lysine autoacetylation.,Yuan H, Rossetto D, Mellert H, Dang W, Srinivasan M, Johnson J, Hodawadekar S, Ding EC, Speicher K, Abshiru N, Perry R, Wu J, Yang C, Zheng YG, Speicher DW, Thibault P, Verreault A, Johnson FB, Berger SL, Sternglanz R, McMahon SB, Cote J, Marmorstein R EMBO J. 2011 Oct 21. doi: 10.1038/emboj.2011.382. PMID:22020126<ref>PMID:22020126</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
==See Also== | ==See Also== | ||
*[[Histone acetyltransferase|Histone acetyltransferase]] | *[[Histone acetyltransferase|Histone acetyltransferase]] | ||
== References == | |||
== | <references/> | ||
< | __TOC__ | ||
</StructureSection> | |||
[[Category: Histone acetyltransferase]] | [[Category: Histone acetyltransferase]] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Ding, E C | [[Category: Ding, E C]] | ||
[[Category: Marmorstein, R | [[Category: Marmorstein, R]] | ||
[[Category: Yuan, H | [[Category: Yuan, H]] | ||
[[Category: Hat domain]] | [[Category: Hat domain]] | ||
[[Category: Myst protein]] | [[Category: Myst protein]] | ||
[[Category: Transferase]] | [[Category: Transferase]] | ||
[[Category: Zinc finger]] | [[Category: Zinc finger]] | ||
Revision as of 18:46, 9 December 2014
Human MOF crystal structure with active site lysine partially acetylatedHuman MOF crystal structure with active site lysine partially acetylated
Structural highlights
Publication Abstract from PubMedThe MYST protein lysine acetyltransferases are evolutionarily conserved throughout eukaryotes and acetylate proteins to regulate diverse biological processes including gene regulation, DNA repair, cell-cycle regulation, stem cell homeostasis and development. Here, we demonstrate that MYST protein acetyltransferase activity requires active site lysine autoacetylation. The X-ray crystal structures of yeast Esa1 (yEsa1/KAT5) bound to a bisubstrate H4K16CoA inhibitor and human MOF (hMOF/KAT8/MYST1) reveal that they are autoacetylated at a strictly conserved lysine residue in MYST proteins (yEsa1-K262 and hMOF-K274) in the enzyme active site. The structure of hMOF also shows partial occupancy of K274 in the unacetylated form, revealing that the side chain reorients to a position that engages the catalytic glutamate residue and would block cognate protein substrate binding. Consistent with the structural findings, we present mass spectrometry data and biochemical experiments to demonstrate that this lysine autoacetylation on yEsa1, hMOF and its yeast orthologue, ySas2 (KAT8) occurs in solution and is required for acetylation and protein substrate binding in vitro. We also show that this autoacetylation occurs in vivo and is required for the cellular functions of these MYST proteins. These findings provide an avenue for the autoposttranslational regulation of MYST proteins that is distinct from other acetyltransferases but draws similarities to the phosphoregulation of protein kinases. MYST protein acetyltransferase activity requires active site lysine autoacetylation.,Yuan H, Rossetto D, Mellert H, Dang W, Srinivasan M, Johnson J, Hodawadekar S, Ding EC, Speicher K, Abshiru N, Perry R, Wu J, Yang C, Zheng YG, Speicher DW, Thibault P, Verreault A, Johnson FB, Berger SL, Sternglanz R, McMahon SB, Cote J, Marmorstein R EMBO J. 2011 Oct 21. doi: 10.1038/emboj.2011.382. PMID:22020126[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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