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| | ==Structure of the alpha-tubulin acetyltransferase, alpha-TAT1== | | ==Structure of the alpha-tubulin acetyltransferase, alpha-TAT1== |
| - | <StructureSection load='4gs4' size='340' side='right' caption='[[4gs4]], [[Resolution|resolution]] 2.11Å' scene=''> | + | <StructureSection load='4gs4' size='340' side='right'caption='[[4gs4]], [[Resolution|resolution]] 2.11Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4gs4]] 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=4GS4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4GS4 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4gs4]] is a 1 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=4GS4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4GS4 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACO:ACETYL+COENZYME+*A'>ACO</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACO:ACETYL+COENZYME+*A'>ACO</scene>, <scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</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=4gs4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gs4 OCA], [https://pdbe.org/4gs4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4gs4 RCSB], [https://www.ebi.ac.uk/pdbsum/4gs4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4gs4 ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ATAT1, C6orf134, MEC17, Nbla00487 ([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/Alpha-tubulin_N-acetyltransferase Alpha-tubulin N-acetyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.1.108 2.3.1.108] </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=4gs4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gs4 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4gs4 RCSB], [http://www.ebi.ac.uk/pdbsum/4gs4 PDBsum]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/ATAT_HUMAN ATAT_HUMAN]] Specifically acetylates 'Lys-40' in alpha-tubulin on the lumenal side of microtubules. May affect microtubule stability and regulate microtubule dynamics. May be involved in neuron development.<ref>PMID:20829795</ref> | + | [https://www.uniprot.org/uniprot/ATAT_HUMAN ATAT_HUMAN] Specifically acetylates 'Lys-40' in alpha-tubulin on the lumenal side of microtubules. May affect microtubule stability and regulate microtubule dynamics. May be involved in neuron development.<ref>PMID:20829795</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| | </div> | | </div> |
| | + | <div class="pdbe-citations 4gs4" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Alpha-tubulin N-acetyltransferase 3D structures|Alpha-tubulin N-acetyltransferase 3D structures]] |
| | + | *[[Tubulin acetyltransferase|Tubulin acetyltransferase]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Alpha-tubulin N-acetyltransferase]] | |
| | [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
| - | [[Category: Fan, J]] | + | [[Category: Large Structures]] |
| - | [[Category: Friedmann, D R]] | + | [[Category: Fan J]] |
| - | [[Category: Marmorstein, R]] | + | [[Category: Friedmann DR]] |
| - | [[Category: Acetyl coenzyme a binding]] | + | [[Category: Marmorstein R]] |
| - | [[Category: Cytosolic]]
| + | |
| - | [[Category: Transferase]]
| + | |
| Structural highlights
Function
ATAT_HUMAN Specifically acetylates 'Lys-40' in alpha-tubulin on the lumenal side of microtubules. May affect microtubule stability and regulate microtubule dynamics. May be involved in neuron development.[1]
Publication Abstract from PubMed
Protein acetylation is an important posttranslational modification with the recent identification of new substrates and enzymes, new links to disease, and modulators of protein acetylation for therapy. alpha-Tubulin acetyltransferase (alphaTAT1) is the major alpha-tubulin lysine-40 (K40) acetyltransferase in mammals, nematodes, and protozoa, and its activity plays a conserved role in several microtubule-based processes. Here, we present the X-ray crystal structure of the human alphaTAT1/acetyl-CoA complex. Together with structure-based mutagenesis, enzymatic analysis, and functional studies in cells, we elucidate the catalytic mechanism and mode of tubulin-specific acetylation. We find that alphaTAT1 has an overall fold similar to the Gcn5 histone acetyltransferase but contains a relatively wide substrate binding groove and unique structural elements that play important roles in alpha-tubulin-specific acetylation. Conserved aspartic acid and cysteine residues play important catalytic roles through a ternary complex mechanism. alphaTAT1 mutations have analogous effects on tubulin acetylation in vitro and in cells, demonstrating that it is the central determining factor of alpha-tubulin K40 acetylation levels in vivo. Together, these studies provide general insights into distinguishing features between histone and tubulin acetyltransferases, and they have specific implications for understanding the molecular basis of tubulin acetylation and for developing small molecule modulators of microtubule acetylation for therapy.
Structure of the alpha-tubulin acetyltransferase, alphaTAT1, and implications for tubulin-specific acetylation.,Friedmann DR, Aguilar A, Fan J, Nachury MV, Marmorstein R Proc Natl Acad Sci U S A. 2012 Nov 27;109(48):19655-60. doi:, 10.1073/pnas.1209357109. Epub 2012 Oct 15. PMID:23071314[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Akella JS, Wloga D, Kim J, Starostina NG, Lyons-Abbott S, Morrissette NS, Dougan ST, Kipreos ET, Gaertig J. MEC-17 is an alpha-tubulin acetyltransferase. Nature. 2010 Sep 9;467(7312):218-22. doi: 10.1038/nature09324. PMID:20829795 doi:10.1038/nature09324
- ↑ Friedmann DR, Aguilar A, Fan J, Nachury MV, Marmorstein R. Structure of the alpha-tubulin acetyltransferase, alphaTAT1, and implications for tubulin-specific acetylation. Proc Natl Acad Sci U S A. 2012 Nov 27;109(48):19655-60. doi:, 10.1073/pnas.1209357109. Epub 2012 Oct 15. PMID:23071314 doi:10.1073/pnas.1209357109
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