5ex3: Difference between revisions
New page: '''Unreleased structure''' The entry 5ex3 is ON HOLD Authors: Qiao, Q., Fu, W., Liu, N., Wang, M., Min, J., Zhu, B., Xu, R.M, Yang, N. Description: Crystal structure of human SMYD3 in ... |
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==Crystal structure of human SMYD3 in complex with a VEGFR1 peptide== | |||
<StructureSection load='5ex3' size='340' side='right'caption='[[5ex3]], [[Resolution|resolution]] 2.41Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5ex3]] 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=5EX3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5EX3 FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.408Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACY:ACETIC+ACID'>ACY</scene>, <scene name='pdbligand=MLY:N-DIMETHYL-LYSINE'>MLY</scene>, <scene name='pdbligand=SAH:S-ADENOSYL-L-HOMOCYSTEINE'>SAH</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=5ex3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ex3 OCA], [https://pdbe.org/5ex3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5ex3 RCSB], [https://www.ebi.ac.uk/pdbsum/5ex3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5ex3 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/SMYD3_HUMAN SMYD3_HUMAN] Histone methyltransferase. Specifically methylates 'Lys-4' and 'Lys-5' of histone H3, inducing di- and tri-methylation, but not monomethylation. Plays an important role in transcriptional activation as a member of an RNA polymerase complex. Binds DNA containing 5'-CCCTCC-3' or 5'-GAGGGG-3' sequences.<ref>PMID:15235609</ref> <ref>PMID:22419068</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
SMYD3 is a SET domain-containing N-lysine methyltransferase associated with multiple cancers. Its reported substrates include histones (H3K4 and H4K5), vascular endothelial growth factor receptor 1 (VEGFR1 Lys(831)) and MAP3 kinase kinase (MAP3K2 Lys(260)). To reveal the structural basis for substrate preference and the catalytic mechanism of SMYD3, we have solved its co-crystal structures with VEGFR1 and MAP3K2 peptides. Our structural and biochemical analyses show that MAP3K2 serves as a robust substrate of SMYD3 because of the presence of a phenylalanine residue at the -2 position. A shallow hydrophobic pocket on SMYD3 accommodates the binding of the phenylalanine and promotes efficient catalytic activities of SMYD3. By contrast, SMYD3 displayed a weak activity toward a VEGFR1 peptide, and the location of the acceptor lysine in the folded kinase domain of VEGFR1 requires drastic conformational rearrangements for juxtaposition of the acceptor lysine with the enzymatic active site. Our results clearly revealed structural determinants for the substrate preference of SMYD3 and provided mechanistic insights into lysine methylation of MAP3K2. The knowledge should be useful for the development of SMYD3 inhibitors in the fight against MAP3K2 and Ras-driven cancer. | |||
Structural Basis for Substrate Preference of SMYD3, a SET Domain-containing Protein Lysine Methyltransferase.,Fu W, Liu N, Qiao Q, Wang M, Min J, Zhu B, Xu RM, Yang N J Biol Chem. 2016 Apr 22;291(17):9173-80. doi: 10.1074/jbc.M115.709832. Epub 2016, Feb 29. PMID:26929412<ref>PMID:26929412</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 5ex3" style="background-color:#fffaf0;"></div> | ||
[[Category: | |||
[[Category: | ==See Also== | ||
[[Category: Min | *[[Histone methyltransferase 3D structures|Histone methyltransferase 3D structures]] | ||
[[Category: Qiao | == References == | ||
[[Category: Xu | <references/> | ||
[[Category: Zhu | __TOC__ | ||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Fu W]] | |||
[[Category: Liu N]] | |||
[[Category: Min J]] | |||
[[Category: Qiao Q]] | |||
[[Category: Wang M]] | |||
[[Category: Xu RM]] | |||
[[Category: Yang N]] | |||
[[Category: Zhu B]] | |||
Latest revision as of 11:30, 12 July 2023
Crystal structure of human SMYD3 in complex with a VEGFR1 peptideCrystal structure of human SMYD3 in complex with a VEGFR1 peptide
Structural highlights
FunctionSMYD3_HUMAN Histone methyltransferase. Specifically methylates 'Lys-4' and 'Lys-5' of histone H3, inducing di- and tri-methylation, but not monomethylation. Plays an important role in transcriptional activation as a member of an RNA polymerase complex. Binds DNA containing 5'-CCCTCC-3' or 5'-GAGGGG-3' sequences.[1] [2] Publication Abstract from PubMedSMYD3 is a SET domain-containing N-lysine methyltransferase associated with multiple cancers. Its reported substrates include histones (H3K4 and H4K5), vascular endothelial growth factor receptor 1 (VEGFR1 Lys(831)) and MAP3 kinase kinase (MAP3K2 Lys(260)). To reveal the structural basis for substrate preference and the catalytic mechanism of SMYD3, we have solved its co-crystal structures with VEGFR1 and MAP3K2 peptides. Our structural and biochemical analyses show that MAP3K2 serves as a robust substrate of SMYD3 because of the presence of a phenylalanine residue at the -2 position. A shallow hydrophobic pocket on SMYD3 accommodates the binding of the phenylalanine and promotes efficient catalytic activities of SMYD3. By contrast, SMYD3 displayed a weak activity toward a VEGFR1 peptide, and the location of the acceptor lysine in the folded kinase domain of VEGFR1 requires drastic conformational rearrangements for juxtaposition of the acceptor lysine with the enzymatic active site. Our results clearly revealed structural determinants for the substrate preference of SMYD3 and provided mechanistic insights into lysine methylation of MAP3K2. The knowledge should be useful for the development of SMYD3 inhibitors in the fight against MAP3K2 and Ras-driven cancer. Structural Basis for Substrate Preference of SMYD3, a SET Domain-containing Protein Lysine Methyltransferase.,Fu W, Liu N, Qiao Q, Wang M, Min J, Zhu B, Xu RM, Yang N J Biol Chem. 2016 Apr 22;291(17):9173-80. doi: 10.1074/jbc.M115.709832. Epub 2016, Feb 29. PMID:26929412[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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