6ict
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==Structure of SETD3 bound to SAH and methylated actin== | ==Structure of SETD3 bound to SAH and methylated actin== | ||
| - | <StructureSection load='6ict' size='340' side='right' caption='[[6ict]], [[Resolution|resolution]] 1.95Å' scene=''> | + | <StructureSection load='6ict' size='340' side='right'caption='[[6ict]], [[Resolution|resolution]] 1.95Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[6ict]] is a 8 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6ICT OCA]. For a <b>guided tour on the structure components</b> use [ | + | <table><tr><td colspan='2'>[[6ict]] is a 8 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=6ICT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6ICT FirstGlance]. <br> |
| - | </td></tr><tr id=' | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.952Å</td></tr> |
| - | <tr id=' | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=HIC:4-METHYL-HISTIDINE'>HIC</scene>, <scene name='pdbligand=SAH:S-ADENOSYL-L-HOMOCYSTEINE'>SAH</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=6ict FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ict OCA], [https://pdbe.org/6ict PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6ict RCSB], [https://www.ebi.ac.uk/pdbsum/6ict PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6ict ProSAT]</span></td></tr> | |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | + | |
</table> | </table> | ||
| - | == Disease == | ||
| - | [[http://www.uniprot.org/uniprot/ACTB_HUMAN ACTB_HUMAN]] Defects in ACTB are a cause of dystonia juvenile-onset (DYTJ) [MIM:[http://omim.org/entry/607371 607371]]. DYTJ is a form of dystonia with juvenile onset. Dystonia is defined by the presence of sustained involuntary muscle contraction, often leading to abnormal postures. DYTJ patients manifest progressive, generalized, dopa-unresponsive dystonia, developmental malformations and sensory hearing loss.<ref>PMID:16685646</ref> Defects in ACTB are the cause of Baraitser-Winter syndrome type 1 (BRWS1) [MIM:[http://omim.org/entry/243310 243310]]. A rare developmental disorder characterized by the combination of congenital ptosis, high-arched eyebrows, hypertelorism, ocular colobomata, and a brain malformation consisting of anterior-predominant lissencephaly. Other typical features include postnatal short stature and microcephaly, intellectual disability, seizures, and hearing loss.<ref>PMID:22366783</ref> | ||
== Function == | == Function == | ||
| - | [ | + | [https://www.uniprot.org/uniprot/SETD3_HUMAN SETD3_HUMAN] Histone methyltransferase that methylates 'Lys-36' of histone H3 (H3K36me). H3 'Lys-36' methylation represents a specific tag for epigenetic transcriptional activation (By similarity). |
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | SETD3 is a member of the SET (Su(var)3-9, Enhancer of zeste, and Trithorax) domain protein superfamily and plays important roles in hypoxic pulmonary hypertension, muscle differentiation, and carcinogenesis. Previously, we identified SETD3 as the actin-specific methyltransferase that methylates the N3 of His73 on beta-actin (Kwiatkowski et al., 2018). Here, we present two structures of S-adenosyl-L-homocysteine-bound SETD3 in complex with either an unmodified beta-actin peptide or its His-methylated variant. Structural analyses, supported by biochemical experiments and enzyme activity assays, indicate that the recognition and methylation of beta-actin by SETD3 are highly sequence specific, and that both SETD3 and beta-actin adopt pronounced conformational changes upon binding to each other. In conclusion, this study is the first to show a catalytic mechanism of SETD3-mediated histidine methylation on beta-actin, which not only throws light on the protein histidine methylation phenomenon but also facilitates the design of small molecule inhibitors of SETD3. | ||
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| + | Structural insights into SETD3-mediated histidine methylation on beta-actin.,Guo Q, Liao S, Kwiatkowski S, Tomaka W, Yu H, Wu G, Tu X, Min J, Drozak J, Xu C Elife. 2019 Feb 20;8. pii: 43676. doi: 10.7554/eLife.43676. PMID:30785395<ref>PMID:30785395</ref> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 6ict" style="background-color:#fffaf0;"></div> | ||
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| + | ==See Also== | ||
| + | *[[Histone methyltransferase 3D structures|Histone methyltransferase 3D structures]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| - | [[Category: | + | [[Category: Homo sapiens]] |
| - | [[Category: | + | [[Category: Large Structures]] |
| - | [[Category: | + | [[Category: Guo Q]] |
| - | [[Category: | + | [[Category: Liao S]] |
| - | [[Category: Xu | + | [[Category: Xu C]] |
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Current revision
Structure of SETD3 bound to SAH and methylated actin
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Categories: Homo sapiens | Large Structures | Guo Q | Liao S | Xu C
