6mb0 - Revision history

OCA at 14:42, 13 March 2024

OCA — Wed, 13 Mar 2024 14:42:08 GMT

←Older revision		Revision as of 14:42, 13 March 2024
Line 3:		Line 3:
	<StructureSection load='6mb0' size='340' side='right'caption='[[6mb0]], [[Resolution\|resolution]] 1.55Å' scene=''>		<StructureSection load='6mb0' size='340' side='right'caption='[[6mb0]], [[Resolution\|resolution]] 1.55Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6mb0]] is a 3 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~Haemamoeba_vivax Haemamoeba~~ vivax]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6MB0 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6MB0 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6mb0]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Plasmodium_vivax Plasmodium vivax]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6MB0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6MB0 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=JCY:1-(5-{4-fluoro-2-[2-(1,3,5-trimethyl-1H-pyrazol-4-yl)ethoxy]phenyl}-1-methyl-1H-indazol-3-yl)-N,N-dimethylmethanamine'>JCY</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=YNC:TETRADEC-13-YNOIC+ACID+-+COA+THIOESTER'>YNC</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]] 1.55Å</td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PVC01_130042700, PVP01_1336100 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=5855 Haemamoeba vivax])</td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=JCY:1-(5-{4-fluoro-2-[2-(1,3,5-trimethyl-1H-pyrazol-4-yl)ethoxy]phenyl}-1-methyl-1H-indazol-3-yl)-N,N-dimethylmethanamine'>JCY</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=YNC:TETRADEC-13-YNOIC+ACID+-+COA+THIOESTER'>YNC</scene></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'>[https://proteopedia.org/fgij/fg.htm?mol=6mb0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6mb0 OCA], [https://pdbe.org/6mb0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6mb0 RCSB], [https://www.ebi.ac.uk/pdbsum/6mb0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6mb0 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=6mb0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6mb0 OCA], [~~http~~://pdbe.org/6mb0 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6mb0 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6mb0 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6mb0 ProSAT]</span></td></tr>	+
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/A0A1G4HIY1_PLAVI A0A1G4HIY1_PLAVI]] Adds a myristoyl group to the N-terminal glycine residue of certain cellular proteins.[RuleBase:RU000586]	+	[https://www.uniprot.org/uniprot/A0A1G4HIY1_PLAVI A0A1G4HIY1_PLAVI] Adds a myristoyl group to the N-terminal glycine residue of certain cellular proteins.[RuleBase:RU000586]
-	~~<div style="background-color:#fffaf0;">~~	+
-	~~== Publication Abstract from PubMed ==~~	+
-	The attachment of myristate to the N-terminal glycine of certain proteins is largely a co-translational modification catalyzed by N-myristoyltransferase (NMT), and involved in protein membrane-localization. Pathogen NMT is a validated therapeutic target in numerous infectious diseases including malaria. In Plasmodium falciparum, NMT substrates are important in essential processes including parasite gliding motility and host cell invasion. Here, we generated parasites resistant to a particular NMT inhibitor series and show that resistance in an in vitro parasite growth assay is mediated by a single amino acid substitution in the NMT substrate-binding pocket. The basis of resistance was validated and analyzed with a structure-guided approach using crystallography, in combination with enzyme activity, stability, and surface plasmon resonance assays, allowing identification of another inhibitor series unaffected by this substitution. We suggest that resistance studies incorporated early in the drug development process help selection of drug combinations to impede rapid evolution of parasite resistance.	+
-		+
-	Structure-Guided Identification of Resistance Breaking Antimalarial NMyristoyltransferase Inhibitors.,Schlott AC, Mayclin S, Reers AR, Coburn-Flynn O, Bell AS, Green J, Knuepfer E, Charter D, Bonnert R, Campo B, Burrows J, Lyons-Abbott S, Staker BL, Chung CW, Myler PJ, Fidock DA, Tate EW, Holder AA Cell Chem Biol. 2019 Apr 9. pii: S2451-9456(19)30111-4. doi:, 10.1016/j.chembiol.2019.03.015. PMID:31080074<ref>PMID:31080074</ref>	+
-		+
-	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~	+
-	~~</div>~~	+
-	~~<div class="pdbe-citations 6mb0" style="background-color:#fffaf0;"></div>~~	+
-	~~== References ==~~	+
-	~~<references/>~~	+
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: Glycylpeptide N-tetradecanoyltransferase]]
-	[[Category: Haemamoeba vivax]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: ~~Structural genomic]]~~	+	[[Category: Plasmodium vivax]]
-	~~[[Category: Glycylpeptide n-tetradecanoyltransferase]]~~	+
-	~~[[Category: N-myristoyltransferase]]~~	+
-	~~[[Category: Nmt]]~~	+
-	~~[[Category: Salvador i]]~~	+
-	~~[[Category: Ssgcid]]~~	+
-	~~[[Category: Transferase~~]]	+

OCA at 06:58, 31 July 2019

OCA — Wed, 31 Jul 2019 06:58:20 GMT

←Older revision		Revision as of 06:58, 31 July 2019
Line 3:		Line 3:
	<StructureSection load='6mb0' size='340' side='right'caption='[[6mb0]], [[Resolution\|resolution]] 1.55Å' scene=''>		<StructureSection load='6mb0' size='340' side='right'caption='[[6mb0]], [[Resolution\|resolution]] 1.55Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6mb0]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6MB0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6MB0 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6mb0]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Haemamoeba_vivax Haemamoeba vivax]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6MB0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6MB0 FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=JCY:1-(5-{4-fluoro-2-[2-(1,3,5-trimethyl-1H-pyrazol-4-yl)ethoxy]phenyl}-1-methyl-1H-indazol-3-yl)-N,N-dimethylmethanamine'>JCY</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=YNC:TETRADEC-13-YNOIC+ACID+-+COA+THIOESTER'>YNC</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=JCY:1-(5-{4-fluoro-2-[2-(1,3,5-trimethyl-1H-pyrazol-4-yl)ethoxy]phenyl}-1-methyl-1H-indazol-3-yl)-N,N-dimethylmethanamine'>JCY</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=YNC:TETRADEC-13-YNOIC+ACID+-+COA+THIOESTER'>YNC</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PVC01_130042700, PVP01_1336100 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=5855 Haemamoeba vivax])</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=6mb0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6mb0 OCA], [http://pdbe.org/6mb0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6mb0 RCSB], [http://www.ebi.ac.uk/pdbsum/6mb0 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6mb0 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=6mb0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6mb0 OCA], [http://pdbe.org/6mb0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6mb0 RCSB], [http://www.ebi.ac.uk/pdbsum/6mb0 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6mb0 ProSAT]</span></td></tr>
Line 24:		Line 25:
	</StructureSection>		</StructureSection>
	[[Category: Glycylpeptide N-tetradecanoyltransferase]]		[[Category: Glycylpeptide N-tetradecanoyltransferase]]
		+	[[Category: Haemamoeba vivax]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Structural genomic]]		[[Category: Structural genomic]]

OCA at 22:47, 5 June 2019

OCA — Wed, 05 Jun 2019 22:47:28 GMT

←Older revision		Revision as of 22:47, 5 June 2019
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 6mb0 is ~~ON HOLD until Aug 29 2020~~	+	==Crystal structure of N-myristoyl transferase (NMT) G386E mutant from Plasmodium vivax in complex with inhibitor IMP-1002==
		+	<StructureSection load='6mb0' size='340' side='right'caption='[[6mb0]], [[Resolution\|resolution]] 1.55Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[6mb0]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6MB0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6MB0 FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=JCY:1-(5-{4-fluoro-2-[2-(1,3,5-trimethyl-1H-pyrazol-4-yl)ethoxy]phenyl}-1-methyl-1H-indazol-3-yl)-N,N-dimethylmethanamine'>JCY</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=YNC:TETRADEC-13-YNOIC+ACID+-+COA+THIOESTER'>YNC</scene></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=6mb0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6mb0 OCA], [http://pdbe.org/6mb0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6mb0 RCSB], [http://www.ebi.ac.uk/pdbsum/6mb0 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6mb0 ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/A0A1G4HIY1_PLAVI A0A1G4HIY1_PLAVI]] Adds a myristoyl group to the N-terminal glycine residue of certain cellular proteins.[RuleBase:RU000586]
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The attachment of myristate to the N-terminal glycine of certain proteins is largely a co-translational modification catalyzed by N-myristoyltransferase (NMT), and involved in protein membrane-localization. Pathogen NMT is a validated therapeutic target in numerous infectious diseases including malaria. In Plasmodium falciparum, NMT substrates are important in essential processes including parasite gliding motility and host cell invasion. Here, we generated parasites resistant to a particular NMT inhibitor series and show that resistance in an in vitro parasite growth assay is mediated by a single amino acid substitution in the NMT substrate-binding pocket. The basis of resistance was validated and analyzed with a structure-guided approach using crystallography, in combination with enzyme activity, stability, and surface plasmon resonance assays, allowing identification of another inhibitor series unaffected by this substitution. We suggest that resistance studies incorporated early in the drug development process help selection of drug combinations to impede rapid evolution of parasite resistance.

-	~~Authors~~: ~~Seattle Structural Genomics Center for Infectious Disease~~ (~~SSGCID~~)	+	Structure-Guided Identification of Resistance Breaking Antimalarial NMyristoyltransferase Inhibitors.,Schlott AC, Mayclin S, Reers AR, Coburn-Flynn O, Bell AS, Green J, Knuepfer E, Charter D, Bonnert R, Campo B, Burrows J, Lyons-Abbott S, Staker BL, Chung CW, Myler PJ, Fidock DA, Tate EW, Holder AA Cell Chem Biol. 2019 Apr 9. pii: S2451-9456(19)30111-4. doi:, 10.1016/j.chembiol.2019.03.015. PMID:31080074<ref>PMID:31080074</ref>

-	~~Description: Crystal structure~~ of N-~~myristoyl transferase (NMT) G386E mutant from Plasmodium vivax in complex with inhibitor IMP~~-~~1002~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased~~ Structures]]	+	</div>
-	[[Category: ~~Seattle~~ Structural ~~Genomics Center For Infectious Disease (~~Ssgcid)]]	+	<div class="pdbe-citations 6mb0" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Glycylpeptide N-tetradecanoyltransferase]]
		+	[[Category: Large Structures]]
		+	[[Category: Structural genomic]]
		+	[[Category: Glycylpeptide n-tetradecanoyltransferase]]
		+	[[Category: N-myristoyltransferase]]
		+	[[Category: Nmt]]
		+	[[Category: Salvador i]]
		+	[[Category: Ssgcid]]
		+	[[Category: Transferase]]

OCA at 06:23, 3 October 2018

OCA — Wed, 03 Oct 2018 06:23:27 GMT

←Older revision		Revision as of 06:23, 3 October 2018
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 6mb0 is ON HOLD	+	The entry 6mb0 is ON HOLD until Aug 29 2020

	Authors: Seattle Structural Genomics Center for Infectious Disease (SSGCID)		Authors: Seattle Structural Genomics Center for Infectious Disease (SSGCID)

OCA: Protected "6mb0" [edit=sysop:move=sysop]

OCA — Wed, 05 Sep 2018 08:54:24 GMT

Protected "6mb0" [edit=sysop:move=sysop]

←Older revision

Revision as of 08:54, 5 September 2018

OCA: New page: '''Unreleased structure''' The entry 6mb0 is ON HOLD Authors: Seattle Structural Genomics Center for Infectious Disease (SSGCID) Description: Crystal structure of N-myristoyl transfera...

OCA — Wed, 05 Sep 2018 08:54:22 GMT

New page: '''Unreleased structure''' The entry 6mb0 is ON HOLD Authors: Seattle Structural Genomics Center for Infectious Disease (SSGCID) Description: Crystal structure of N-myristoyl transfera...

New page

'''Unreleased structure'''

The entry 6mb0 is ON HOLD

Authors: Seattle Structural Genomics Center for Infectious Disease (SSGCID)

Description: Crystal structure of N-myristoyl transferase (NMT) G386E mutant from Plasmodium vivax in complex with inhibitor IMP-1002
[[Category: Unreleased Structures]]
[[Category: Seattle Structural Genomics Center For Infectious Disease (Ssgcid)]]