6aqu - Revision history

OCA at 14:23, 4 October 2023

OCA — Wed, 04 Oct 2023 14:23:17 GMT

←Older revision		Revision as of 14:23, 4 October 2023
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	<StructureSection load='6aqu' size='340' side='right'caption='[[6aqu]], [[Resolution\|resolution]] 2.60Å' scene=''>		<StructureSection load='6aqu' size='340' side='right'caption='[[6aqu]], [[Resolution\|resolution]] 2.60Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6aqu]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6AQU OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=6AQU FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6aqu]] is a 2 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=6AQU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6AQU 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>~~</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]] 2.6Å</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></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=6aqu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6aqu OCA], [~~http~~://pdbe.org/6aqu PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6aqu RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6aqu PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6aqu 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=6aqu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6aqu OCA], [https://pdbe.org/6aqu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6aqu RCSB], [https://www.ebi.ac.uk/pdbsum/6aqu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6aqu ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/PNPH_PLAF7 PNPH_PLAF7] 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:18957439, PubMed:14982926, PubMed:16131758, PubMed:19575810, PubMed:24416224, PubMed:29440412). Preferentially acts on inosine and guanosine, and to a lesser extent on 2'-deoxyguanosine and guanosine (PubMed:14982926, PubMed:16131758, PubMed:19575810). 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 (PubMed:18957439, PubMed:14982926, PubMed:24416224). Generates hypoxanthine from both the purine salvage pathway and from polyamine metabolism which is required for nucleic acids synthesis (PubMed:18957439, PubMed:14982926, PubMed:24416224). Has no activity towards adenosine (By similarity).[UniProtKB:Q8T9Z7]<ref>PMID:14982926</ref> <ref>PMID:16131758</ref> <ref>PMID:18957439</ref> <ref>PMID:19575810</ref> <ref>PMID:24416224</ref> <ref>PMID:29440412</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: Almo, S C]]
-	[[Category: Bonanno, J B]]
-	[[Category: Ducati, R G]]
-	[[Category: Harijan, R K]]
-	[[Category: Namanja-Magliano, H A]]
-	[[Category: Schramm, V L]]
-	[[Category: Drug resistant pnp]]
	[[Category: Plasmodium falciparum]]		[[Category: Plasmodium falciparum]]
-	[[Category: ~~Pnp mutation~~]]	+	[[Category: Almo SC]]
-	[[Category: ~~Transferase~~]]	+	[[Category: Bonanno JB]]
		+	[[Category: Ducati RG]]
		+	[[Category: Harijan RK]]
		+	[[Category: Namanja-Magliano HA]]
		+	[[Category: Schramm VL]]

OCA at 21:30, 28 October 2020

OCA — Wed, 28 Oct 2020 21:30:48 GMT

←Older revision		Revision as of 21:30, 28 October 2020
Line 1:		Line 1:

	==Crystal Structure of Plasmodium falciparum purine nucleoside phosphorylase: The M183L mutant==		==Crystal Structure of Plasmodium falciparum purine nucleoside phosphorylase: The M183L mutant==
-	<StructureSection load='6aqu' size='340' side='right' caption='[[6aqu]], [[Resolution\|resolution]] 2.60Å' scene=''>	+	<StructureSection load='6aqu' size='340' side='right'caption='[[6aqu]], [[Resolution\|resolution]] 2.60Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6aqu]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6AQU OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6AQU FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6aqu]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6AQU OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6AQU 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></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></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=6aqu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6aqu OCA], [http://pdbe.org/6aqu PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6aqu RCSB], [http://www.ebi.ac.uk/pdbsum/6aqu PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6aqu 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=6aqu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6aqu OCA], [http://pdbe.org/6aqu PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6aqu RCSB], [http://www.ebi.ac.uk/pdbsum/6aqu PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6aqu 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 6aqu" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 6aqu" 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: Almo, S C]]		[[Category: Almo, S C]]

OCA at 06:36, 28 March 2018

OCA — Wed, 28 Mar 2018 06:36:42 GMT

←Older revision		Revision as of 06:36, 28 March 2018
Line 1:		Line 1:
-	'''Unreleased structure'''

-	The ~~entry~~ 6aqu is ~~ON HOLD until Paper~~ Publication	+	==Crystal Structure of Plasmodium falciparum purine nucleoside phosphorylase: The M183L mutant==
		+	<StructureSection load='6aqu' size='340' side='right' caption='[[6aqu]], [[Resolution\|resolution]] 2.60Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[6aqu]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6AQU OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6AQU 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></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=6aqu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6aqu OCA], [http://pdbe.org/6aqu PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6aqu RCSB], [http://www.ebi.ac.uk/pdbsum/6aqu PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6aqu ProSAT]</span></td></tr>
		+	</table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Plasmodium falciparum causes the most lethal form of human malaria and is a global health concern. The parasite responds to antimalarial therapies by developing drug resistance. The continuous development of new antimalarials with novel mechanisms of action is a priority for drug combination therapies. The use of transition-state analog inhibitors to block essential steps in purine salvage has been proposed as a new antimalarial approach. Mutations that reduce transition-state analog binding are also expected to reduce the essential catalytic function of the target. We have previously reported that inhibition of host and P. falciparum purine nucleoside phosphorylase (PfPNP) by DADMe-Immucillin-G (DADMe-ImmG) causes purine starvation and parasite death in vitro and in primate infection models. P. falciparum cultured under incremental DADMe-ImmG drug pressure initially exhibited increased PfPNP gene copy number and protein expression. At increased drug pressure, additional PfPNP gene copies appeared with point mutations at catalytic site residues involved in drug binding. Mutant PfPNPs from resistant clones demonstrated reduced affinity for DADMe-ImmG, but also reduced catalytic efficiency. The catalytic defects were partially overcome by gene amplification in the region expressing PfPNP. Crystal structures of native and mutated PfPNPs demonstrate altered catalytic site contacts to DADMe-ImmG. Both point mutations and gene amplification are required to overcome purine starvation induced by DADMe-ImmG. Resistance developed slowly, over 136 generations (2(136) clonal selection). Transition-state analog inhibitors against PfPNP are slow to induce resistance and may have promise in malaria therapy.

-	~~Authors: Harijan, R.K~~., Ducati~~, R.G.~~, Namanja-Magliano, ~~H.A.~~, ~~Bonanno~~, ~~J.B.~~, ~~Almo~~, S.C., ~~Schramm, V~~.L.	+	Genetic resistance to purine nucleoside phosphorylase inhibition in Plasmodium falciparum.,Ducati RG, Namanja-Magliano HA, Harijan RK, Fajardo JE, Fiser A, Daily JP, Schramm VL Proc Natl Acad Sci U S A. 2018 Feb 12. pii: 1525670115. doi:, 10.1073/pnas.1525670115. PMID:29440412<ref>PMID:29440412</ref>

-	~~Description: Crystal Structure~~ of ~~Plasmodium falciparum purine nucleoside phosphorylase~~: ~~The M183L mutant~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased Structures~~]]	+	</div>
-	[[Category: Almo, S.C]]	+	<div class="pdbe-citations 6aqu" style="background-color:#fffaf0;"></div>
-	[[Category: ~~Schramm~~, ~~V.L~~]]	+	== References ==
-	[[Category: Harijan, R.K]]	+	<references/>
-	[[Category: Namanja-Magliano, H.A]]	+	__TOC__
-	[[Category: ~~Bonanno~~, ~~J.B~~]]	+	</StructureSection>
-	[[Category: ~~Ducati, R.G~~]]	+	[[Category: Purine-nucleoside phosphorylase]]
		+	[[Category: Almo, S C]]
		+	[[Category: Bonanno, J B]]
		+	[[Category: Ducati, R G]]
		+	[[Category: Harijan, R K]]
		+	[[Category: Namanja-Magliano, H A]]
		+	[[Category: Schramm, V L]]
		+	[[Category: Drug resistant pnp]]
		+	[[Category: Plasmodium falciparum]]
		+	[[Category: Pnp mutation]]
		+	[[Category: Transferase]]

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

OCA — Wed, 27 Sep 2017 16:41:38 GMT

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

←Older revision

Revision as of 16:41, 27 September 2017

OCA: New page: '''Unreleased structure''' The entry 6aqu is ON HOLD until Paper Publication Authors: Harijan, R.K., Ducati, R.G., Namanja-Magliano, H.A., Bonanno, J.B., Almo, S.C., Schramm, V.L. Desc...

OCA — Wed, 27 Sep 2017 16:41:37 GMT

New page: '''Unreleased structure''' The entry 6aqu is ON HOLD until Paper Publication Authors: Harijan, R.K., Ducati, R.G., Namanja-Magliano, H.A., Bonanno, J.B., Almo, S.C., Schramm, V.L. Desc...

New page

'''Unreleased structure'''

The entry 6aqu is ON HOLD until Paper Publication

Authors: Harijan, R.K., Ducati, R.G., Namanja-Magliano, H.A., Bonanno, J.B., Almo, S.C., Schramm, V.L.

Description: Crystal Structure of Plasmodium falciparum purine nucleoside phosphorylase: The M183L mutant
[[Category: Unreleased Structures]]
[[Category: Almo, S.C]]
[[Category: Schramm, V.L]]
[[Category: Harijan, R.K]]
[[Category: Namanja-Magliano, H.A]]
[[Category: Bonanno, J.B]]
[[Category: Ducati, R.G]]