8a12 - Revision history

OCA at 08:08, 7 February 2024

OCA — Wed, 07 Feb 2024 08:08:01 GMT

←Older revision		Revision as of 08:08, 7 February 2024
Line 10:		Line 10:
	== Function ==		== Function ==
	[https://www.uniprot.org/uniprot/MYOA_PLAF7 MYOA_PLAF7] Myosins are actin-based motor molecules with ATPase activity. Unconventional myosins serve in intracellular movements. Their highly divergent tails are presumed to bind to membranous compartments, which would be moved relative to actin filaments (By similarity).		[https://www.uniprot.org/uniprot/MYOA_PLAF7 MYOA_PLAF7] Myosins are actin-based motor molecules with ATPase activity. Unconventional myosins serve in intracellular movements. Their highly divergent tails are presumed to bind to membranous compartments, which would be moved relative to actin filaments (By similarity).
-	<div style="background-color:#fffaf0;">
-	== Publication Abstract from PubMed ==
-	Malaria results in more than 500,000 deaths per year and the causative Plasmodium parasites continue to develop resistance to all known agents, including different antimalarial combinations. The class XIV myosin motor PfMyoA is part of a core macromolecular complex called the glideosome, essential for Plasmodium parasite mobility and therefore an attractive drug target. Here, we characterize the interaction of a small molecule (KNX-002) with PfMyoA. KNX-002 inhibits PfMyoA ATPase activity in vitro and blocks asexual blood stage growth of merozoites, one of three motile Plasmodium life-cycle stages. Combining biochemical assays and X-ray crystallography, we demonstrate that KNX-002 inhibits PfMyoA using a previously undescribed binding mode, sequestering it in a post-rigor state detached from actin. KNX-002 binding prevents efficient ATP hydrolysis and priming of the lever arm, thus inhibiting motor activity. This small-molecule inhibitor of PfMyoA paves the way for the development of alternative antimalarial treatments.
-
-	Mechanism of small molecule inhibition of Plasmodium falciparum myosin A informs antimalarial drug design.,Moussaoui D, Robblee JP, Robert-Paganin J, Auguin D, Fisher F, Fagnant PM, Macfarlane JE, Schaletzky J, Wehri E, Mueller-Dieckmann C, Baum J, Trybus KM, Houdusse A Nat Commun. 2023 Jun 12;14(1):3463. doi: 10.1038/s41467-023-38976-7. PMID:37308472<ref>PMID:37308472</ref>
-
-	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	</div>
-	<div class="pdbe-citations 8a12" style="background-color:#fffaf0;"></div>
-	== References ==
-	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>

OCA at 11:23, 15 November 2023

OCA — Wed, 15 Nov 2023 11:23:08 GMT

←Older revision		Revision as of 11:23, 15 November 2023
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[8a12]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Plasmodium_falciparum Plasmodium falciparum]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8A12 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8A12 FirstGlance]. <br>		<table><tr><td colspan='2'>[[8a12]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Plasmodium_falciparum Plasmodium falciparum]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8A12 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8A12 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 2.03Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=8a12 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8a12 OCA], [https://pdbe.org/8a12 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8a12 RCSB], [https://www.ebi.ac.uk/pdbsum/8a12 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8a12 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=8a12 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8a12 OCA], [https://pdbe.org/8a12 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8a12 RCSB], [https://www.ebi.ac.uk/pdbsum/8a12 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8a12 ProSAT]</span></td></tr>
	</table>		</table>

OCA at 09:36, 21 June 2023

OCA — Wed, 21 Jun 2023 09:36:16 GMT

←Older revision		Revision as of 09:36, 21 June 2023
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 8a12 is ~~ON HOLD until Paper~~ Publication	+	==Plasmodium falciparum Myosin A full-length, post-rigor state complexed to Mg.ATP-gamma-S==
		+	<StructureSection load='8a12' size='340' side='right'caption='[[8a12]], [[Resolution\|resolution]] 2.03Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[8a12]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Plasmodium_falciparum Plasmodium falciparum]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8A12 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8A12 FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=8a12 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8a12 OCA], [https://pdbe.org/8a12 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8a12 RCSB], [https://www.ebi.ac.uk/pdbsum/8a12 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8a12 ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/MYOA_PLAF7 MYOA_PLAF7] Myosins are actin-based motor molecules with ATPase activity. Unconventional myosins serve in intracellular movements. Their highly divergent tails are presumed to bind to membranous compartments, which would be moved relative to actin filaments (By similarity).
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Malaria results in more than 500,000 deaths per year and the causative Plasmodium parasites continue to develop resistance to all known agents, including different antimalarial combinations. The class XIV myosin motor PfMyoA is part of a core macromolecular complex called the glideosome, essential for Plasmodium parasite mobility and therefore an attractive drug target. Here, we characterize the interaction of a small molecule (KNX-002) with PfMyoA. KNX-002 inhibits PfMyoA ATPase activity in vitro and blocks asexual blood stage growth of merozoites, one of three motile Plasmodium life-cycle stages. Combining biochemical assays and X-ray crystallography, we demonstrate that KNX-002 inhibits PfMyoA using a previously undescribed binding mode, sequestering it in a post-rigor state detached from actin. KNX-002 binding prevents efficient ATP hydrolysis and priming of the lever arm, thus inhibiting motor activity. This small-molecule inhibitor of PfMyoA paves the way for the development of alternative antimalarial treatments.

-	~~Authors: Moussaoui~~, D., Robblee, J~~.P.~~, Auguin, D., Fisher, F., Fagnant, ~~P.M.~~, ~~MacFarlane~~, J.E., Mueller-Dieckmann, C., Baum, J~~., Robert-Paganin, J.~~, Trybus~~, K.M.~~, Houdusse, A.	+	Mechanism of small molecule inhibition of Plasmodium falciparum myosin A informs antimalarial drug design.,Moussaoui D, Robblee JP, Robert-Paganin J, Auguin D, Fisher F, Fagnant PM, Macfarlane JE, Schaletzky J, Wehri E, Mueller-Dieckmann C, Baum J, Trybus KM, Houdusse A Nat Commun. 2023 Jun 12;14(1):3463. doi: 10.1038/s41467-023-38976-7. PMID:37308472<ref>PMID:37308472</ref>

-	~~Description: Plasmodium falciparum Myosin A full-length~~, ~~post-rigor state complexed to Mg~~.~~ATP~~-~~gamma~~-S	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased~~ Structures]]	+	</div>
-	[[Category: Auguin, D]]	+	<div class="pdbe-citations 8a12" style="background-color:#fffaf0;"></div>
-	[[Category: Baum, J]]	+	== References ==
-	[[Category: Fisher, F]]	+	<references/>
-	[[Category: ~~Trybus, K.M~~]]	+	__TOC__
-	[[Category: ~~Robblee, J.P~~]]	+	</StructureSection>
-	[[Category: Moussaoui, D]]	+	[[Category: Large Structures]]
-	[[Category: ~~Fagnant, P.M~~]]	+	[[Category: Plasmodium falciparum]]
-	[[Category: ~~Houdusse, A~~]]	+	[[Category: Auguin D]]
-	[[Category: Robert-Paganin, J]]	+	[[Category: Baum J]]
-	[[Category: ~~Mueller-Dieckmann, C]]~~	+	[[Category: Fagnant PM]]
-	~~[[Category: Macfarlane, J.E~~]]	+	[[Category: Fisher F]]
		+	[[Category: Houdusse A]]
		+	[[Category: MacFarlane JE]]
		+	[[Category: Moussaoui D]]
		+	[[Category: Mueller-Dieckmann C]]
		+	[[Category: Robblee JP]]
		+	[[Category: Robert-Paganin J]]
		+	[[Category: Trybus KM]]

OCA at 05:21, 31 August 2022

OCA — Wed, 31 Aug 2022 05:21:30 GMT

←Older revision		Revision as of 05:21, 31 August 2022
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 8a12 is ON HOLD	+	The entry 8a12 is ON HOLD until Paper Publication

	Authors: Moussaoui, D., Robblee, J.P., Auguin, D., Fisher, F., Fagnant, P.M., MacFarlane, J.E., Mueller-Dieckmann, C., Baum, J., Robert-Paganin, J., Trybus, K.M., Houdusse, A.		Authors: Moussaoui, D., Robblee, J.P., Auguin, D., Fisher, F., Fagnant, P.M., MacFarlane, J.E., Mueller-Dieckmann, C., Baum, J., Robert-Paganin, J., Trybus, K.M., Houdusse, A.

OCA: Protected "8a12" [edit=sysop:move=sysop]

OCA — Wed, 08 Jun 2022 04:22:18 GMT

Protected "8a12" [edit=sysop:move=sysop]

←Older revision

Revision as of 04:22, 8 June 2022

OCA: New page: '''Unreleased structure''' The entry 8a12 is ON HOLD Authors: Moussaoui, D., Robblee, J.P., Auguin, D., Fisher, F., Fagnant, P.M., MacFarlane, J.E., Mueller-Dieckmann, C., Baum, J., Rob...

OCA — Wed, 08 Jun 2022 04:22:17 GMT

New page: '''Unreleased structure''' The entry 8a12 is ON HOLD Authors: Moussaoui, D., Robblee, J.P., Auguin, D., Fisher, F., Fagnant, P.M., MacFarlane, J.E., Mueller-Dieckmann, C., Baum, J., Rob...

New page

'''Unreleased structure'''

The entry 8a12 is ON HOLD

Authors: Moussaoui, D., Robblee, J.P., Auguin, D., Fisher, F., Fagnant, P.M., MacFarlane, J.E., Mueller-Dieckmann, C., Baum, J., Robert-Paganin, J., Trybus, K.M., Houdusse, A.

Description: Plasmodium falciparum Myosin A full-length, post-rigor state complexed to Mg.ATP-gamma-S
[[Category: Unreleased Structures]]
[[Category: Auguin, D]]
[[Category: Baum, J]]
[[Category: Fisher, F]]
[[Category: Trybus, K.M]]
[[Category: Robblee, J.P]]
[[Category: Moussaoui, D]]
[[Category: Fagnant, P.M]]
[[Category: Houdusse, A]]
[[Category: Robert-Paganin, J]]
[[Category: Mueller-Dieckmann, C]]
[[Category: Macfarlane, J.E]]