5v37 - Revision history

OCA at 14:30, 6 March 2024

OCA — Wed, 06 Mar 2024 14:30:53 GMT

←Older revision		Revision as of 14:30, 6 March 2024
Line 3:		Line 3:
	<StructureSection load='5v37' size='340' side='right'caption='[[5v37]], [[Resolution\|resolution]] 1.42Å' scene=''>		<StructureSection load='5v37' size='340' side='right'caption='[[5v37]], [[Resolution\|resolution]] 1.42Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5v37]] is a 1 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~Human Human~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5V37 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5V37 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5v37]] 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=5V37 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5V37 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=8WD:N-{(3-endo)-8-[(trans-4-aminocyclohexyl)sulfonyl]-8-azabicyclo[3.2.1]octan-3-yl}-5-cyclopropyl-1,2-oxazole-3-carboxamide'>8WD</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=SAM:S-ADENOSYLMETHIONINE'>SAM</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]] 1.42Å</td></tr>
-	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5v3h\|5v3h]]</td></tr>~~	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=8WD:N-{(3-endo)-8-[(trans-4-aminocyclohexyl)sulfonyl]-8-azabicyclo[3.2.1]octan-3-yl}-5-cyclopropyl-1,2-oxazole-3-carboxamide'>8WD</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=SAM:S-ADENOSYLMETHIONINE'>SAM</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">SMYD3, ZMYND1, ZNFN3A1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=5v37 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5v37 OCA], [https://pdbe.org/5v37 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5v37 RCSB], [https://www.ebi.ac.uk/pdbsum/5v37 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5v37 ProSAT]</span></td></tr>
-	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Histone-lysine_N-methyltransferase Histone-lysine N-methyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.1.43 2.1.1.43] </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=5v37 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5v37 OCA], [~~http~~://pdbe.org/5v37 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5v37 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5v37 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5v37 ProSAT]</span></td></tr>	+
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://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>	+	[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 ==~~	+
-	A key challenge in the development of precision medicine is defining the phenotypic consequences of pharmacological modulation of specific target macromolecules. To address this issue, a variety of genetic, molecular and chemical tools can be used. All of these approaches can produce misleading results if the specificity of the tools is not well understood and the proper controls are not performed. In this paper we illustrate these general themes by providing detailed studies of small molecule inhibitors of the enzymatic activity of two members of the SMYD branch of the protein lysine methyltransferases, SMYD2 and SMYD3. We show that tool compounds as well as CRISPR/Cas9 fail to reproduce many of the cell proliferation findings associated with SMYD2 and SMYD3 inhibition previously obtained with RNAi based approaches and with early stage chemical probes.	+
-		+
-	Small molecule inhibitors and CRISPR/Cas9 mutagenesis demonstrate that SMYD2 and SMYD3 activity are dispensable for autonomous cancer cell proliferation.,Thomenius MJ, Totman J, Harvey D, Mitchell LH, Riera TV, Cosmopoulos K, Grassian AR, Klaus C, Foley M, Admirand EA, Jahic H, Majer C, Wigle T, Jacques SL, Gureasko J, Brach D, Lingaraj T, West K, Smith S, Rioux N, Waters NJ, Tang C, Raimondi A, Munchhof M, Mills JE, Ribich S, Porter Scott M, Kuntz KW, Janzen WP, Moyer M, Smith JJ, Chesworth R, Copeland RA, Boriack-Sjodin PA PLoS One. 2018 Jun 1;13(6):e0197372. doi: 10.1371/journal.pone.0197372., eCollection 2018. PMID:29856759<ref>PMID:29856759</ref>	+
-		+
-	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~	+
-	~~</div>~~	+
-	~~<div class="pdbe-citations 5v37" style="background-color:#fffaf0;"></div~~>	+

	==See Also==		==See Also==
-	*[[Histone methyltransferase\|Histone methyltransferase]]	+	*[[Histone methyltransferase 3D structures\|Histone methyltransferase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Histone-lysine N-methyltransferase]]~~	+	[[Category: Homo sapiens]]
-	~~[[Category: Human~~]]	+
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Boriack-Sjodin~~, P A]]~~	+	[[Category: Boriack-Sjodin PA]]
-	~~[[Category: Protein lysine methyltransferase]]~~	+
-	~~[[Category: Protein-inhibitor complex]]~~	+
-	~~[[Category: Transferase-transferase inhibitor complex~~]]	+

OCA at 13:20, 10 May 2019

OCA — Fri, 10 May 2019 13:20:30 GMT

←Older revision		Revision as of 13:20, 10 May 2019
Line 1:		Line 1:

	==Crystal structure of SMYD3 with SAM and EPZ028862==		==Crystal structure of SMYD3 with SAM and EPZ028862==
-	<StructureSection load='5v37' size='340' side='right' caption='[[5v37]], [[Resolution\|resolution]] 1.42Å' scene=''>	+	<StructureSection load='5v37' size='340' side='right'caption='[[5v37]], [[Resolution\|resolution]] 1.42Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5v37]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5V37 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5V37 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5v37]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5V37 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5V37 FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=8WD:N-{(3-endo)-8-[(trans-4-aminocyclohexyl)sulfonyl]-8-azabicyclo[3.2.1]octan-3-yl}-5-cyclopropyl-1,2-oxazole-3-carboxamide'>8WD</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=SAM:S-ADENOSYLMETHIONINE'>SAM</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=8WD:N-{(3-endo)-8-[(trans-4-aminocyclohexyl)sulfonyl]-8-azabicyclo[3.2.1]octan-3-yl}-5-cyclopropyl-1,2-oxazole-3-carboxamide'>8WD</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=SAM:S-ADENOSYLMETHIONINE'>SAM</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5v3h\|5v3h]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5v3h\|5v3h]]</td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">SMYD3, ZMYND1, ZNFN3A1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Histone-lysine_N-methyltransferase Histone-lysine N-methyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.1.43 2.1.1.43] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Histone-lysine_N-methyltransferase Histone-lysine N-methyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.1.43 2.1.1.43] </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=5v37 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5v37 OCA], [http://pdbe.org/5v37 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5v37 RCSB], [http://www.ebi.ac.uk/pdbsum/5v37 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5v37 ProSAT]</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=5v37 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5v37 OCA], [http://pdbe.org/5v37 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5v37 RCSB], [http://www.ebi.ac.uk/pdbsum/5v37 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5v37 ProSAT]</span></td></tr>
Line 11:		Line 12:
	== Function ==		== Function ==
	[[http://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>		[[http://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 ==
		+	A key challenge in the development of precision medicine is defining the phenotypic consequences of pharmacological modulation of specific target macromolecules. To address this issue, a variety of genetic, molecular and chemical tools can be used. All of these approaches can produce misleading results if the specificity of the tools is not well understood and the proper controls are not performed. In this paper we illustrate these general themes by providing detailed studies of small molecule inhibitors of the enzymatic activity of two members of the SMYD branch of the protein lysine methyltransferases, SMYD2 and SMYD3. We show that tool compounds as well as CRISPR/Cas9 fail to reproduce many of the cell proliferation findings associated with SMYD2 and SMYD3 inhibition previously obtained with RNAi based approaches and with early stage chemical probes.
		+
		+	Small molecule inhibitors and CRISPR/Cas9 mutagenesis demonstrate that SMYD2 and SMYD3 activity are dispensable for autonomous cancer cell proliferation.,Thomenius MJ, Totman J, Harvey D, Mitchell LH, Riera TV, Cosmopoulos K, Grassian AR, Klaus C, Foley M, Admirand EA, Jahic H, Majer C, Wigle T, Jacques SL, Gureasko J, Brach D, Lingaraj T, West K, Smith S, Rioux N, Waters NJ, Tang C, Raimondi A, Munchhof M, Mills JE, Ribich S, Porter Scott M, Kuntz KW, Janzen WP, Moyer M, Smith JJ, Chesworth R, Copeland RA, Boriack-Sjodin PA PLoS One. 2018 Jun 1;13(6):e0197372. doi: 10.1371/journal.pone.0197372., eCollection 2018. PMID:29856759<ref>PMID:29856759</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 5v37" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Histone methyltransferase\|Histone methyltransferase]]
	== References ==		== References ==
	<references/>		<references/>
Line 16:		Line 29:
	</StructureSection>		</StructureSection>
	[[Category: Histone-lysine N-methyltransferase]]		[[Category: Histone-lysine N-methyltransferase]]
		+	[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Boriack-Sjodin, P A]]		[[Category: Boriack-Sjodin, P A]]
	[[Category: Protein lysine methyltransferase]]		[[Category: Protein lysine methyltransferase]]
	[[Category: Protein-inhibitor complex]]		[[Category: Protein-inhibitor complex]]
	[[Category: Transferase-transferase inhibitor complex]]		[[Category: Transferase-transferase inhibitor complex]]

OCA at 05:01, 8 March 2018

OCA — Thu, 08 Mar 2018 05:01:51 GMT

←Older revision		Revision as of 05:01, 8 March 2018
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 5v37 is ~~ON HOLD~~ ~~until Paper Publication~~	+	==Crystal structure of SMYD3 with SAM and EPZ028862==
-		+	<StructureSection load='5v37' size='340' side='right' caption='[[5v37]], [[Resolution\|resolution]] 1.42Å' scene=''>
-	~~Authors~~:	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[5v37]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5V37 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5V37 FirstGlance]. <br>
-	~~Description~~:	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=8WD:N-{(3-endo)-8-[(trans-4-aminocyclohexyl)sulfonyl]-8-azabicyclo[3.2.1]octan-3-yl}-5-cyclopropyl-1,2-oxazole-3-carboxamide'>8WD</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=SAM:S-ADENOSYLMETHIONINE'>SAM</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
-	[[Category: ~~Unreleased Structures~~]]	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5v3h\|5v3h]]</td></tr>
		+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Histone-lysine_N-methyltransferase Histone-lysine N-methyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.1.43 2.1.1.43] </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=5v37 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5v37 OCA], [http://pdbe.org/5v37 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5v37 RCSB], [http://www.ebi.ac.uk/pdbsum/5v37 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5v37 ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://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>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Histone-lysine N-methyltransferase]]
		+	[[Category: Boriack-Sjodin, P A]]
		+	[[Category: Protein lysine methyltransferase]]
		+	[[Category: Protein-inhibitor complex]]
		+	[[Category: Transferase-transferase inhibitor complex]]

OCA at 11:03, 19 April 2017

OCA — Wed, 19 Apr 2017 11:03:05 GMT

←Older revision		Revision as of 11:03, 19 April 2017
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 5v37 is ON HOLD	+	The entry 5v37 is ON HOLD until Paper Publication

	Authors:		Authors:

OCA: Protected "5v37" [edit=sysop:move=sysop]

OCA — Wed, 15 Mar 2017 19:41:57 GMT

Protected "5v37" [edit=sysop:move=sysop]

←Older revision

Revision as of 19:41, 15 March 2017

OCA: New page: '''Unreleased structure''' The entry 5v37 is ON HOLD Authors: Description: Category: Unreleased Structures

OCA — Wed, 15 Mar 2017 19:41:56 GMT

New page: '''Unreleased structure''' The entry 5v37 is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 5v37 is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]