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6mon

From Proteopedia

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Crystal structure of human SMYD2 in complex with Nle-peptide inhibitor

Structural highlights

6mon is a 4 chain structure with sequence from Homo sapiens and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.711Å
Ligands:	, , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

SMYD2_HUMAN Protein-lysine N-methyltransferase that methylates both histones and non-histone proteins. Specifically methylates histone H3 'Lys-4' (H3K4me) and dimethylates histone H3 'Lys-36' (H3K36me2). Has also methyltransferase activity toward non-histone proteins such as p53/TP53 and RB1. Monomethylates 'Lys-370' of p53/TP53, leading to decreased DNA-binding activity and subsequent transcriptional regulation activity of p53/TP53. Monomethylates 'Lys-860' of RB1/RB.^[1] ^[2] ^[3] ^[4]

Publication Abstract from PubMed

Lysine methylation is a key regulator of histone protein function. Beyond histones, few connections have been made to the enzymes responsible for the deposition of these posttranslational modifications. Here, we debut a high-throughput functional proteomics platform that maps the sequence determinants of lysine methyltransferase (KMT) substrate selectivity without a priori knowledge of a substrate or target proteome. We demonstrate the predictive power of this approach for identifying KMT substrates, generating scaffolds for inhibitor design, and predicting the impact of missense mutations on lysine methylation signaling. By comparing KMT selectivity profiles to available lysine methylome datasets, we reveal a disconnect between preferred KMT substrates and the ability to detect these motifs using standard mass spectrometry pipelines. Collectively, our studies validate the use of this platform for guiding the study of lysine methylation signaling and suggest that substantial gaps exist in proteome-wide curation of lysine methylomes.

A functional proteomics platform to reveal the sequence determinants of lysine methyltransferase substrate selectivity.,Cornett EM, Dickson BM, Krajewski K, Spellmon N, Umstead A, Vaughan RM, Shaw KM, Versluis PP, Cowles MW, Brunzelle J, Yang Z, Vega IE, Sun ZW, Rothbart SB Sci Adv. 2018 Nov 28;4(11):eaav2623. doi: 10.1126/sciadv.aav2623. eCollection, 2018 Nov. PMID:30498785^[5]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Huang J, Perez-Burgos L, Placek BJ, Sengupta R, Richter M, Dorsey JA, Kubicek S, Opravil S, Jenuwein T, Berger SL. Repression of p53 activity by Smyd2-mediated methylation. Nature. 2006 Nov 30;444(7119):629-32. Epub 2006 Nov 15. PMID:17108971 doi:10.1038/nature05287
↑ Huang J, Sengupta R, Espejo AB, Lee MG, Dorsey JA, Richter M, Opravil S, Shiekhattar R, Bedford MT, Jenuwein T, Berger SL. p53 is regulated by the lysine demethylase LSD1. Nature. 2007 Sep 6;449(7158):105-8. PMID:17805299 doi:nature06092
↑ Abu-Farha M, Lambert JP, Al-Madhoun AS, Elisma F, Skerjanc IS, Figeys D. The tale of two domains: proteomics and genomics analysis of SMYD2, a new histone methyltransferase. Mol Cell Proteomics. 2008 Mar;7(3):560-72. Epub 2007 Dec 7. PMID:18065756 doi:10.1074/mcp.M700271-MCP200
↑ Saddic LA, West LE, Aslanian A, Yates JR 3rd, Rubin SM, Gozani O, Sage J. Methylation of the retinoblastoma tumor suppressor by SMYD2. J Biol Chem. 2010 Nov 26;285(48):37733-40. doi: 10.1074/jbc.M110.137612. Epub, 2010 Sep 24. PMID:20870719 doi:10.1074/jbc.M110.137612
↑ Cornett EM, Dickson BM, Krajewski K, Spellmon N, Umstead A, Vaughan RM, Shaw KM, Versluis PP, Cowles MW, Brunzelle J, Yang Z, Vega IE, Sun ZW, Rothbart SB. A functional proteomics platform to reveal the sequence determinants of lysine methyltransferase substrate selectivity. Sci Adv. 2018 Nov 28;4(11):eaav2623. doi: 10.1126/sciadv.aav2623. eCollection, 2018 Nov. PMID:30498785 doi:http://dx.doi.org/10.1126/sciadv.aav2623

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6mon"

@@ Line 1: / Line 1: @@
 ==Crystal structure of human SMYD2 in complex with Nle-peptide inhibitor==
-<StructureSection load='6mon' size='340' side='right' caption='[[6mon]], [[Resolution|resolution]] 2.71&Aring;' scene=''>
+<StructureSection load='6mon' size='340' side='right'caption='[[6mon]], [[Resolution|resolution]] 2.71&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6mon]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6MON OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6MON FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6mon]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6MON OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6MON FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SAH:S-ADENOSYL-L-HOMOCYSTEINE'>SAH</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]] 2.711&#8491;</td></tr>
-<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=NLE:NORLEUCINE'>NLE</scene></td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NLE:NORLEUCINE'>NLE</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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6mon FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6mon OCA], [http://pdbe.org/6mon PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6mon RCSB], [http://www.ebi.ac.uk/pdbsum/6mon PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6mon 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=6mon FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6mon OCA], [https://pdbe.org/6mon PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6mon RCSB], [https://www.ebi.ac.uk/pdbsum/6mon PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6mon ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/SMYD2_HUMAN SMYD2_HUMAN]] Protein-lysine N-methyltransferase that methylates both histones and non-histone proteins. Specifically methylates histone H3 'Lys-4' (H3K4me) and dimethylates histone H3 'Lys-36' (H3K36me2). Has also methyltransferase activity toward non-histone proteins such as p53/TP53 and RB1. Monomethylates 'Lys-370' of p53/TP53, leading to decreased DNA-binding activity and subsequent transcriptional regulation activity of p53/TP53. Monomethylates 'Lys-860' of RB1/RB.<ref>PMID:17108971</ref> <ref>PMID:17805299</ref> <ref>PMID:18065756</ref> <ref>PMID:20870719</ref>
+[https://www.uniprot.org/uniprot/SMYD2_HUMAN SMYD2_HUMAN] Protein-lysine N-methyltransferase that methylates both histones and non-histone proteins. Specifically methylates histone H3 'Lys-4' (H3K4me) and dimethylates histone H3 'Lys-36' (H3K36me2). Has also methyltransferase activity toward non-histone proteins such as p53/TP53 and RB1. Monomethylates 'Lys-370' of p53/TP53, leading to decreased DNA-binding activity and subsequent transcriptional regulation activity of p53/TP53. Monomethylates 'Lys-860' of RB1/RB.<ref>PMID:17108971</ref> <ref>PMID:17805299</ref> <ref>PMID:18065756</ref> <ref>PMID:20870719</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 19: / Line 19: @@
 </div>
 <div class="pdbe-citations 6mon" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Histone methyltransferase 3D structures|Histone methyltransferase 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Brunzelle, J]]
+[[Category: Homo sapiens]]
-[[Category: Cornett, E]]
+[[Category: Large Structures]]
-[[Category: Rothbart, S]]
+[[Category: Synthetic construct]]
-[[Category: Spellmon, N]]
+[[Category: Brunzelle J]]
-[[Category: Yang, Z]]
+[[Category: Cornett E]]
-[[Category: Complex]]
+[[Category: Rothbart S]]
-[[Category: Methyltransferase]]
+[[Category: Spellmon N]]
-[[Category: Norleucine]]
+[[Category: Yang Z]]
-[[Category: Transferase]]

6mon

From Proteopedia

Current revision

Crystal structure of human SMYD2 in complex with Nle-peptide inhibitor

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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