OCA at 14:05, 18 October 2023

2023-10-18T14:05:28Z

←Older revision		Revision as of 14:05, 18 October 2023
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-	'''Unreleased structure'''

-	~~The entry~~ 8fbq is ~~ON HOLD until Paper~~ Publication	+	==Crystal structure of Plasmodium vivax glycylpeptide N-tetradecanoyltransferase (N-myristoyltransferase, NMT) bound to myristoyl-CoA and inhibitor 12b==
		+	<StructureSection load='8fbq' size='340' side='right'caption='[[8fbq]], [[Resolution\|resolution]] 1.65Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[8fbq]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Plasmodium_vivax_Sal-1 Plasmodium vivax Sal-1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8FBQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8FBQ 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]] 1.65Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1PE:PENTAETHYLENE+GLYCOL'>1PE</scene>, <scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MYA:TETRADECANOYL-COA'>MYA</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=XOQ:1-[(3M)-3-{3-[2-(1,3,5-trimethyl-1H-pyrazol-4-yl)ethoxy]pyridin-2-yl}phenyl]piperazine'>XOQ</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=8fbq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8fbq OCA], [https://pdbe.org/8fbq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8fbq RCSB], [https://www.ebi.ac.uk/pdbsum/8fbq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8fbq ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/A5K1A2_PLAVS A5K1A2_PLAVS] Adds a myristoyl group to the N-terminal glycine residue of certain cellular proteins (By similarity).[RuleBase:RU000586]
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Drugs targeting multiple stages of the Plasmodium vivax life cycle are needed to reduce the health and economic burdens caused by malaria worldwide. N-myristoyltransferase (NMT) is an essential eukaryotic enzyme and a validated drug target for combating malaria. However, previous PvNMT inhibitors have failed due to their low selectivity over human NMTs. Herein, we apply a structure-guided hybridization approach combining chemical moieties of previously reported NMT inhibitors to develop the next generation of PvNMT inhibitors. A high-resolution crystal structure of PvNMT bound to a representative selective hybrid compound reveals a unique binding site architecture that includes a selective conformation of a key tyrosine residue. The hybridized compounds significantly decrease P. falciparum blood-stage parasite load and consistently exhibit dose-dependent inhibition of P. vivax liver stage schizonts and hypnozoites. Our data demonstrate that hybridized NMT inhibitors can be multistage antimalarials, targeting dormant and developing forms of liver and blood stage.

-	~~Authors~~:	+	Identification of potent and selective N-myristoyltransferase inhibitors of Plasmodium vivax liver stage hypnozoites and schizonts.,Rodriguez-Hernandez D, Vijayan K, Zigweid R, Fenwick MK, Sankaran B, Roobsoong W, Sattabongkot J, Glennon EKK, Myler PJ, Sunnerhagen P, Staker BL, Kaushansky A, Grotli M Nat Commun. 2023 Sep 5;14(1):5408. doi: 10.1038/s41467-023-41119-7. PMID:37669940<ref>PMID:37669940</ref>

-	~~Description~~:	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased~~ Structures]]	+	</div>
		+	<div class="pdbe-citations 8fbq" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Plasmodium vivax Sal-1]]
		+	[[Category: Early J]]
		+	[[Category: Fenwick MK]]
		+	[[Category: Lovell SW]]
		+	[[Category: Myler PJ]]
		+	[[Category: Phan IQ]]
		+	[[Category: Staker BL]]

OCA at 05:48, 11 January 2023

2023-01-11T05:48:18Z

←Older revision		Revision as of 05:48, 11 January 2023
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 8fbq is ON HOLD	+	The entry 8fbq is ON HOLD until Paper Publication

	Authors:		Authors:

OCA: Protected "8fbq" [edit=sysop:move=sysop]

2022-12-07T05:41:11Z

Protected "8fbq" [edit=sysop:move=sysop]

←Older revision

Revision as of 05:41, 7 December 2022

OCA: New page: '''Unreleased structure''' The entry 8fbq is ON HOLD Authors: Description: Category: Unreleased Structures

2022-12-07T05:41:09Z

New page: '''Unreleased structure''' The entry 8fbq is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 8fbq is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]

8fbq - Revision history

OCA at 14:05, 18 October 2023

OCA at 05:48, 11 January 2023

OCA: Protected "8fbq" [edit=sysop:move=sysop]

OCA: New page: '''Unreleased structure''' The entry 8fbq is ON HOLD Authors: Description: Category: Unreleased Structures