5znc - Revision history

OCA at 09:01, 22 November 2023

OCA — Wed, 22 Nov 2023 09:01:32 GMT

←Older revision		Revision as of 09:01, 22 November 2023
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	<StructureSection load='5znc' size='340' side='right'caption='[[5znc]], [[Resolution\|resolution]] 1.66Å' scene=''>		<StructureSection load='5znc' size='340' side='right'caption='[[5znc]], [[Resolution\|resolution]] 1.66Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5znc]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5ZNC OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=5ZNC FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5znc]] is a 1 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=5ZNC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5ZNC FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat" id="~~ligandDat~~">~~<scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>~~, ~~<scene name='pdbligand=QI9:QUININE'>QI9</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]] 1.66Å</td></tr>
-	<tr id='~~activity~~'><td class="sblockLbl"><b>~~Activity~~:</b></td><td class="sblockDat"><~~span class~~='~~plainlinks~~'>~~[http:~~/~~/en.wikipedia.org/wiki/Purine-nucleoside_phosphorylase Purine-nucleoside phosphorylase]~~, ~~with EC number [http~~:~~//www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.2.1 2.4.2.1]~~ </~~span~~></td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=QI9:QUININE'>QI9</scene></td></tr>
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://proteopedia.org/fgij/fg.htm?mol=5znc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5znc OCA], [~~http~~://pdbe.org/5znc PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5znc RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5znc PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5znc 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=5znc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5znc OCA], [https://pdbe.org/5znc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5znc RCSB], [https://www.ebi.ac.uk/pdbsum/5znc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5znc ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/PNPH_PLAFA PNPH_PLAFA] As part of the purine salvage pathway, catalyzes the phosphorolytic breakdown of the N-glycosidic bond in the beta-(deoxy)ribonucleoside molecules, with the formation of the corresponding free purine bases and pentose-1-phosphate (PubMed:11707439, PubMed:30602534). Preferentially acts on inosine and guanosine, and to a lesser extent on 2'-deoxyinosine and 2'-deoxyguanosine (PubMed:11707439). Also catalyzes the phosphorylation of S-methyl-5'-thioinosine (MTI) to hypoxanthine; MTI is produced by adenosine deaminase (ADA)-mediated breakdown of S-methyl-5'-thioadenosine (MTA), a major by-product of polyamine biosynthesis (By similarity). Generates hypoxanthine from both the purine salvage pathway and from polyamine metabolism which is required for nucleic acids synthesis (By similarity). Has no activity towards adenosine (PubMed:11707439).[UniProtKB:Q8I3X4]<ref>PMID:11707439</ref> <ref>PMID:30602534</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
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	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: ~~Purine-nucleoside phosphorylase~~]]	+	[[Category: Plasmodium falciparum]]
-	[[Category: Chen, D]]	+	[[Category: Chen D]]
-	[[Category: Nordlund, P]]	+	[[Category: Nordlund P]]
-	~~[[Category: Nucleoside phosphorylase]]~~	+
-	~~[[Category: Transferase~~]]	+

OCA at 21:21, 28 October 2020

OCA — Wed, 28 Oct 2020 21:21:50 GMT

←Older revision		Revision as of 21:21, 28 October 2020
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	==Plasmodium falciparum purine nucleoside phosphorylase in complex with quinine==		==Plasmodium falciparum purine nucleoside phosphorylase in complex with quinine==
-	<StructureSection load='5znc' size='340' side='right' caption='[[5znc]], [[Resolution\|resolution]] 1.66Å' scene=''>	+	<StructureSection load='5znc' size='340' side='right'caption='[[5znc]], [[Resolution\|resolution]] 1.66Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5znc]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5ZNC OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5ZNC FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5znc]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5ZNC OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5ZNC FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=QI9:QUININE'>QI9</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=QI9:QUININE'>QI9</scene></td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Purine-nucleoside_phosphorylase Purine-nucleoside phosphorylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.2.1 2.4.2.1] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Purine-nucleoside_phosphorylase Purine-nucleoside phosphorylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.2.1 2.4.2.1] </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=5znc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5znc OCA], [http://pdbe.org/5znc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5znc RCSB], [http://www.ebi.ac.uk/pdbsum/5znc PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5znc ProSAT]</span></td></tr>	+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5znc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5znc OCA], [http://pdbe.org/5znc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5znc RCSB], [http://www.ebi.ac.uk/pdbsum/5znc PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5znc ProSAT]</span></td></tr>
	</table>		</table>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
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	</div>		</div>
	<div class="pdbe-citations 5znc" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5znc" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Purine nucleoside phosphorylase 3D structures\|Purine nucleoside phosphorylase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Large Structures]]
	[[Category: Purine-nucleoside phosphorylase]]		[[Category: Purine-nucleoside phosphorylase]]
	[[Category: Chen, D]]		[[Category: Chen, D]]

OCA at 11:58, 16 January 2019

OCA — Wed, 16 Jan 2019 11:58:52 GMT

←Older revision		Revision as of 11:58, 16 January 2019
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-	'''Unreleased structure'''

-	~~The entry~~ 5znc is ~~ON HOLD until Paper~~ Publication	+	==Plasmodium falciparum purine nucleoside phosphorylase in complex with quinine==
		+	<StructureSection load='5znc' size='340' side='right' caption='[[5znc]], [[Resolution\|resolution]] 1.66Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[5znc]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5ZNC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5ZNC FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=QI9:QUININE'>QI9</scene></td></tr>
		+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Purine-nucleoside_phosphorylase Purine-nucleoside phosphorylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.2.1 2.4.2.1] </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=5znc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5znc OCA], [http://pdbe.org/5znc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5znc RCSB], [http://www.ebi.ac.uk/pdbsum/5znc PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5znc ProSAT]</span></td></tr>
		+	</table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Mechanisms of action (MoAs) have been elusive for most antimalarial drugs in clinical use. Decreasing responsiveness to antimalarial treatments stresses the need for a better resolved understanding of their MoAs and associated resistance mechanisms. In the present work, we implemented the cellular thermal shift assay coupled with mass spectrometry (MS-CETSA) for drug target identification in Plasmodium falciparum, the main causative agent of human malaria. We validated the efficacy of this approach for pyrimethamine, a folic acid antagonist, and E64d, a broad-spectrum cysteine proteinase inhibitor. Subsequently, we applied MS-CETSA to quinine and mefloquine, two important antimalarial drugs with poorly characterized MoAs. Combining studies in the P. falciparum parasite lysate and intact infected red blood cells, we found P. falciparum purine nucleoside phosphorylase (PfPNP) as a common binding target for these two quinoline drugs. Biophysical and structural studies with a recombinant protein further established that both compounds bind within the enzyme's active site. Quinine binds to PfPNP at low nanomolar affinity, suggesting a substantial contribution to its therapeutic effect. Overall, we demonstrated that implementation of MS-CETSA for P. falciparum constitutes a promising strategy to elucidate the MoAs of existing and candidate antimalarial drugs.

-	~~Authors: Chen~~, D., ~~Nordlund~~, P.	+	Identifying purine nucleoside phosphorylase as the target of quinine using cellular thermal shift assay.,Dziekan JM, Yu H, Chen D, Dai L, Wirjanata G, Larsson A, Prabhu N, Sobota RM, Bozdech Z, Nordlund P Sci Transl Med. 2019 Jan 2;11(473). pii: 11/473/eaau3174. doi:, 10.1126/scitranslmed.aau3174. PMID:30602534<ref>PMID:30602534</ref>

-	~~Description: Plasmodium falciparum purine nucleoside phosphorylase in complex with quinine~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[Category~~: ~~Unreleased Structures]]~~	+	</div>
-	[[Category: ~~Nordlund, P~~]]	+	<div class="pdbe-citations 5znc" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Purine-nucleoside phosphorylase]]
	[[Category: Chen, D]]		[[Category: Chen, D]]
		+	[[Category: Nordlund, P]]
		+	[[Category: Nucleoside phosphorylase]]
		+	[[Category: Transferase]]

OCA at 03:50, 25 April 2018

OCA — Wed, 25 Apr 2018 03:50:01 GMT

←Older revision		Revision as of 03:50, 25 April 2018
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

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

	Authors: Chen, D., Nordlund, P.		Authors: Chen, D., Nordlund, P.

-	Description: ~~plasmodium~~ falciparum purine nucleoside phosphorylase in complex with quinine	+	Description: Plasmodium falciparum purine nucleoside phosphorylase in complex with quinine
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
	[[Category: Nordlund, P]]		[[Category: Nordlund, P]]
	[[Category: Chen, D]]		[[Category: Chen, D]]

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

OCA — Wed, 18 Apr 2018 04:04:40 GMT

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

←Older revision

Revision as of 04:04, 18 April 2018

OCA: New page: '''Unreleased structure''' The entry 5znc is ON HOLD Authors: Chen, D., Nordlund, P. Description: plasmodium falciparum purine nucleoside phosphorylase in complex with quinine [[Catego...

OCA — Wed, 18 Apr 2018 04:04:38 GMT

New page: '''Unreleased structure''' The entry 5znc is ON HOLD Authors: Chen, D., Nordlund, P. Description: plasmodium falciparum purine nucleoside phosphorylase in complex with quinine [[Catego...

New page

'''Unreleased structure'''

The entry 5znc is ON HOLD

Authors: Chen, D., Nordlund, P.

Description: plasmodium falciparum purine nucleoside phosphorylase in complex with quinine
[[Category: Unreleased Structures]]
[[Category: Nordlund, P]]
[[Category: Chen, D]]