5mu6 - Revision history

OCA at 17:49, 8 November 2023

OCA — Wed, 08 Nov 2023 17:49:56 GMT

←Older revision		Revision as of 17:49, 8 November 2023
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	==Human N-myristoyltransferase (NMT1) with Myristoyl-CoA and IMP-1088 inhibitor bound==		==Human N-myristoyltransferase (NMT1) with Myristoyl-CoA and IMP-1088 inhibitor bound==
-	<StructureSection load='5mu6' size='340' side='right' caption='[[5mu6]], [[Resolution\|resolution]] 1.88Å' scene=''>	+	<StructureSection load='5mu6' size='340' side='right'caption='[[5mu6]], [[Resolution\|resolution]] 1.88Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5mu6]] is a 2 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=5MU6 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5MU6 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5mu6]] 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=5MU6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5MU6 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=KFK:1-[5-[3,4-bis(fluoranyl)-2-[2-(1,3,5-trimethylpyrazol-4-yl)ethoxy]phenyl]-1-methyl-indazol-3-yl]-~{N},~{N}-dimethyl-methanamine'>KFK</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=MYA:TETRADECANOYL-COA'>MYA</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]] 1.88Å</td></tr>
-	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4c2y\|4c2y]], [[4c2z\|4c2z]]</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=KFK:1-[5-[3,4-bis(fluoranyl)-2-[2-(1,3,5-trimethylpyrazol-4-yl)ethoxy]phenyl]-1-methyl-indazol-3-yl]-~{N},~{N}-dimethyl-methanamine'>KFK</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=MYA:TETRADECANOYL-COA'>MYA</scene></td></tr>
-	~~<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">NMT1, NMT ([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=5mu6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5mu6 OCA], [https://pdbe.org/5mu6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5mu6 RCSB], [https://www.ebi.ac.uk/pdbsum/5mu6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5mu6 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/Glycylpeptide_N-tetradecanoyltransferase Glycylpeptide N-tetradecanoyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.1.97 2.3.1.97] </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=5mu6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5mu6 OCA], [~~http~~://pdbe.org/5mu6 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5mu6 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5mu6 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5mu6 ProSAT]</span></td></tr>	+
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/NMT1_HUMAN NMT1_HUMAN]] Adds a myristoyl group to the N-terminal glycine residue of certain cellular and viral proteins.	+	[https://www.uniprot.org/uniprot/NMT1_HUMAN NMT1_HUMAN] Adds a myristoyl group to the N-terminal glycine residue of certain cellular and viral proteins.
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 25:		Line 23:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Glycylpeptide N-tetradecanoyltransferase~~]]	+	[[Category: Homo sapiens]]
-	[[Category: ~~Human~~]]	+	[[Category: Large Structures]]
-	[[Category: Bell~~, A S~~]]	+	[[Category: Bell AS]]
-	[[Category: Perez-Dorado, I]]	+	[[Category: Perez-Dorado I]]
-	[[Category: Tate~~, E W]]~~	+	[[Category: Tate EW]]
-	~~[[Category: Inhibitor]]~~	+
-	~~[[Category: N-myristoylation]]~~	+
-	~~[[Category: Rhinovirus capsule assembly]]~~	+
-	~~[[Category: Transferase~~]]	+

OCA at 07:36, 23 May 2018

OCA — Wed, 23 May 2018 07:36:44 GMT

←Older revision		Revision as of 07:36, 23 May 2018
Line 3:		Line 3:
	<StructureSection load='5mu6' size='340' side='right' caption='[[5mu6]], [[Resolution\|resolution]] 1.88Å' scene=''>		<StructureSection load='5mu6' size='340' side='right' caption='[[5mu6]], [[Resolution\|resolution]] 1.88Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5mu6]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5MU6 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5MU6 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5mu6]] is a 2 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=5MU6 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5MU6 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=KFK:1-[5-[3,4-bis(fluoranyl)-2-[2-(1,3,5-trimethylpyrazol-4-yl)ethoxy]phenyl]-1-methyl-indazol-3-yl]-~{N},~{N}-dimethyl-methanamine'>KFK</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=MYA:TETRADECANOYL-COA'>MYA</scene></td></tr>		</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=KFK:1-[5-[3,4-bis(fluoranyl)-2-[2-(1,3,5-trimethylpyrazol-4-yl)ethoxy]phenyl]-1-methyl-indazol-3-yl]-~{N},~{N}-dimethyl-methanamine'>KFK</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=MYA:TETRADECANOYL-COA'>MYA</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4c2y\|4c2y]], [[4c2z\|4c2z]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4c2y\|4c2y]], [[4c2z\|4c2z]]</td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">NMT1, NMT ([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/Glycylpeptide_N-tetradecanoyltransferase Glycylpeptide N-tetradecanoyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.1.97 2.3.1.97] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Glycylpeptide_N-tetradecanoyltransferase Glycylpeptide N-tetradecanoyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.1.97 2.3.1.97] </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=5mu6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5mu6 OCA], [http://pdbe.org/5mu6 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5mu6 RCSB], [http://www.ebi.ac.uk/pdbsum/5mu6 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5mu6 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=5mu6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5mu6 OCA], [http://pdbe.org/5mu6 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5mu6 RCSB], [http://www.ebi.ac.uk/pdbsum/5mu6 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5mu6 ProSAT]</span></td></tr>
Line 11:		Line 12:
	== Function ==		== Function ==
	[[http://www.uniprot.org/uniprot/NMT1_HUMAN NMT1_HUMAN]] Adds a myristoyl group to the N-terminal glycine residue of certain cellular and viral proteins.		[[http://www.uniprot.org/uniprot/NMT1_HUMAN NMT1_HUMAN]] Adds a myristoyl group to the N-terminal glycine residue of certain cellular and viral proteins.
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Rhinoviruses (RVs) are the pathogens most often responsible for the common cold, and are a frequent cause of exacerbations in asthma, chronic obstructive pulmonary disease and cystic fibrosis. Here we report the discovery of IMP-1088, a picomolar dual inhibitor of the human N-myristoyltransferases NMT1 and NMT2, and use it to demonstrate that pharmacological inhibition of host-cell N-myristoylation rapidly and completely prevents rhinoviral replication without inducing cytotoxicity. The identification of cooperative binding between weak-binding fragments led to rapid inhibitor optimization through fragment reconstruction, structure-guided fragment linking and conformational control over linker geometry. We show that inhibition of the co-translational myristoylation of a specific virus-encoded protein (VP0) by IMP-1088 potently blocks a key step in viral capsid assembly, to deliver a low nanomolar antiviral activity against multiple RV strains, poliovirus and foot and-mouth disease virus, and protection of cells against virus-induced killing, highlighting the potential of host myristoylation as a drug target in picornaviral infections.
		+
		+	Fragment-derived inhibitors of human N-myristoyltransferase block capsid assembly and replication of the common cold virus.,Mousnier A, Bell AS, Swieboda DP, Morales-Sanfrutos J, Perez-Dorado I, Brannigan JA, Newman J, Ritzefeld M, Hutton JA, Guedan A, Asfor AS, Robinson SW, Hopkins-Navratilova I, Wilkinson AJ, Johnston SL, Leatherbarrow RJ, Tuthill TJ, Solari R, Tate EW Nat Chem. 2018 May 14. pii: 10.1038/s41557-018-0039-2. doi:, 10.1038/s41557-018-0039-2. PMID:29760414<ref>PMID:29760414</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 5mu6" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: Glycylpeptide N-tetradecanoyltransferase]]		[[Category: Glycylpeptide N-tetradecanoyltransferase]]
		+	[[Category: Human]]
	[[Category: Bell, A S]]		[[Category: Bell, A S]]
	[[Category: Perez-Dorado, I]]		[[Category: Perez-Dorado, I]]

OCA at 06:21, 15 February 2018

OCA — Thu, 15 Feb 2018 06:21:22 GMT

←Older revision		Revision as of 06:21, 15 February 2018
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 5mu6 is ~~ON HOLD until Paper Publication~~	+	==Human N-myristoyltransferase (NMT1) with Myristoyl-CoA and IMP-1088 inhibitor bound==
-		+	<StructureSection load='5mu6' size='340' side='right' caption='[[5mu6]], [[Resolution\|resolution]] 1.88Å' scene=''>
-	~~Authors~~: ~~Perez~~-~~Dorado~~, I., ~~Bell~~, A.S., ~~Tate~~, E.W.	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[5mu6]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5MU6 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5MU6 FirstGlance]. <br>
-	~~Description~~: ~~Human~~ N-~~myristoyltransferase (NMT1) with Myristoyl-CoA~~ and ~~IMP-1088 inhibitor bound~~	+	</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=KFK:1-[5-[3,4-bis(fluoranyl)-2-[2-(1,3,5-trimethylpyrazol-4-yl)ethoxy]phenyl]-1-methyl-indazol-3-yl]-~{N},~{N}-dimethyl-methanamine'>KFK</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=MYA:TETRADECANOYL-COA'>MYA</scene></td></tr>
-	[[Category: ~~Unreleased Structures~~]]	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4c2y\|4c2y]], [[4c2z\|4c2z]]</td></tr>
-	[[Category: ~~Tate~~, ~~E.W~~]]	+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Glycylpeptide_N-tetradecanoyltransferase Glycylpeptide N-tetradecanoyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.1.97 2.3.1.97] </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=5mu6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5mu6 OCA], [http://pdbe.org/5mu6 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5mu6 RCSB], [http://www.ebi.ac.uk/pdbsum/5mu6 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5mu6 ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/NMT1_HUMAN NMT1_HUMAN]] Adds a myristoyl group to the N-terminal glycine residue of certain cellular and viral proteins.
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Glycylpeptide N-tetradecanoyltransferase]]
		+	[[Category: Bell, A S]]
	[[Category: Perez-Dorado, I]]		[[Category: Perez-Dorado, I]]
-	[[Category: ~~Bell~~, ~~A.S~~]]	+	[[Category: Tate, E W]]
		+	[[Category: Inhibitor]]
		+	[[Category: N-myristoylation]]
		+	[[Category: Rhinovirus capsule assembly]]
		+	[[Category: Transferase]]

OCA at 11:39, 9 March 2017

OCA — Thu, 09 Mar 2017 11:39:31 GMT

←Older revision		Revision as of 11:39, 9 March 2017
Line 7:		Line 7:
	Description: Human N-myristoyltransferase (NMT1) with Myristoyl-CoA and IMP-1088 inhibitor bound		Description: Human N-myristoyltransferase (NMT1) with Myristoyl-CoA and IMP-1088 inhibitor bound
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
-	[[Category: Perez-Dorado, I]]
	[[Category: Tate, E.W]]		[[Category: Tate, E.W]]
		+	[[Category: Perez-Dorado, I]]
	[[Category: Bell, A.S]]		[[Category: Bell, A.S]]

OCA at 20:34, 25 January 2017

OCA — Wed, 25 Jan 2017 20:34:17 GMT

←Older revision		Revision as of 20:34, 25 January 2017
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 5mu6 is ON HOLD	+	The entry 5mu6 is ON HOLD until Paper Publication

	Authors: Perez-Dorado, I., Bell, A.S., Tate, E.W.		Authors: Perez-Dorado, I., Bell, A.S., Tate, E.W.

OCA: Protected "5mu6" [edit=sysop:move=sysop]

OCA — Wed, 18 Jan 2017 13:17:15 GMT

Protected "5mu6" [edit=sysop:move=sysop]

←Older revision

Revision as of 13:17, 18 January 2017

OCA: New page: '''Unreleased structure''' The entry 5mu6 is ON HOLD Authors: Perez-Dorado, I., Bell, A.S., Tate, E.W. Description: Human N-myristoyltransferase (NMT1) with Myristoyl-CoA and IMP-1088 ...

OCA — Wed, 18 Jan 2017 13:17:14 GMT

New page: '''Unreleased structure''' The entry 5mu6 is ON HOLD Authors: Perez-Dorado, I., Bell, A.S., Tate, E.W. Description: Human N-myristoyltransferase (NMT1) with Myristoyl-CoA and IMP-1088 ...

New page

'''Unreleased structure'''

The entry 5mu6 is ON HOLD

Authors: Perez-Dorado, I., Bell, A.S., Tate, E.W.

Description: Human N-myristoyltransferase (NMT1) with Myristoyl-CoA and IMP-1088 inhibitor bound
[[Category: Unreleased Structures]]
[[Category: Perez-Dorado, I]]
[[Category: Tate, E.W]]
[[Category: Bell, A.S]]