6aqs - Revision history

OCA at 14:23, 4 October 2023

OCA — Wed, 04 Oct 2023 14:23:14 GMT

←Older revision		Revision as of 14:23, 4 October 2023
Line 1:		Line 1:

	==Crystal structure of Plasmodium falciparum purine nucleoside phosphorylase (V181D) mutant complexed with DADMe-ImmG and phosphate==		==Crystal structure of Plasmodium falciparum purine nucleoside phosphorylase (V181D) mutant complexed with DADMe-ImmG and phosphate==
-	<StructureSection load='6aqs' size='340' side='right' caption='[[6aqs]], [[Resolution\|resolution]] 1.57Å' scene=''>	+	<StructureSection load='6aqs' size='340' side='right'caption='[[6aqs]], [[Resolution\|resolution]] 1.57Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6aqs]] is a 1 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~Plafa Plafa~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6AQS OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6AQS FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6aqs]] 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=6AQS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6AQS FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=IM5:2-AMINO-7-{[(3R,4R)-3-HYDROXY-4-(HYDROXYMETHYL)PYRROLIDIN-1-YL]METHYL}-3,5-DIHYDRO-4H-PYRROLO[3,2-D]PYRIMIDIN-4-ONE'>IM5</scene>, <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]] 1.57Å</td></tr>
-	~~<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PNP ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=5833 PLAFA])</td></tr>~~	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=IM5:2-AMINO-7-{[(3R,4R)-3-HYDROXY-4-(HYDROXYMETHYL)PYRROLIDIN-1-YL]METHYL}-3,5-DIHYDRO-4H-PYRROLO[3,2-D]PYRIMIDIN-4-ONE'>IM5</scene>, <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'>[https://proteopedia.org/fgij/fg.htm?mol=6aqs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6aqs OCA], [https://pdbe.org/6aqs PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6aqs RCSB], [https://www.ebi.ac.uk/pdbsum/6aqs PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6aqs 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=6aqs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6aqs OCA], [~~http~~://pdbe.org/6aqs PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6aqs RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6aqs PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6aqs 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 ==
Line 18:		Line 19:
	</div>		</div>
	<div class="pdbe-citations 6aqs" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 6aqs" 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: ~~Plafa]]~~	+	[[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: Dadme-immg]]~~	+
-	~~[[Category: Phosphorylase~~]]	+
	[[Category: Plasmodium falciparum]]		[[Category: Plasmodium falciparum]]
-	[[Category: ~~Pnp mutant~~]]	+	[[Category: Almo SC]]
-	[[Category: ~~Transferase~~]]	+	[[Category: Bonanno JB]]
		+	[[Category: Ducati RG]]
		+	[[Category: Harijan RK]]
		+	[[Category: Namanja-Magliano HA]]
		+	[[Category: Schramm VL]]

OCA at 07:14, 28 February 2018

OCA — Wed, 28 Feb 2018 07:14:01 GMT

←Older revision		Revision as of 07:14, 28 February 2018
Line 3:		Line 3:
	<StructureSection load='6aqs' size='340' side='right' caption='[[6aqs]], [[Resolution\|resolution]] 1.57Å' scene=''>		<StructureSection load='6aqs' size='340' side='right' caption='[[6aqs]], [[Resolution\|resolution]] 1.57Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6aqs]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6AQS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6AQS FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6aqs]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Plafa Plafa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6AQS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6AQS FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=IM5:2-AMINO-7-{[(3R,4R)-3-HYDROXY-4-(HYDROXYMETHYL)PYRROLIDIN-1-YL]METHYL}-3,5-DIHYDRO-4H-PYRROLO[3,2-D]PYRIMIDIN-4-ONE'>IM5</scene>, <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"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=IM5:2-AMINO-7-{[(3R,4R)-3-HYDROXY-4-(HYDROXYMETHYL)PYRROLIDIN-1-YL]METHYL}-3,5-DIHYDRO-4H-PYRROLO[3,2-D]PYRIMIDIN-4-ONE'>IM5</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PNP ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=5833 PLAFA])</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=6aqs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6aqs OCA], [http://pdbe.org/6aqs PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6aqs RCSB], [http://www.ebi.ac.uk/pdbsum/6aqs PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6aqs 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=6aqs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6aqs OCA], [http://pdbe.org/6aqs PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6aqs RCSB], [http://www.ebi.ac.uk/pdbsum/6aqs PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6aqs ProSAT]</span></td></tr>
	</table>		</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.
		+
		+	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>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 6aqs" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Plafa]]
	[[Category: Purine-nucleoside phosphorylase]]		[[Category: Purine-nucleoside phosphorylase]]
	[[Category: Almo, S C]]		[[Category: Almo, S C]]

OCA at 06:32, 15 February 2018

OCA — Thu, 15 Feb 2018 06:32:14 GMT

←Older revision		Revision as of 06:32, 15 February 2018
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 6aqs ~~is ON HOLD until Paper Publication~~	+	==Crystal structure of Plasmodium falciparum purine nucleoside phosphorylase (V181D) mutant complexed with DADMe-ImmG and phosphate==
-		+	<StructureSection load='6aqs' size='340' side='right' caption='[[6aqs]], [[Resolution\|resolution]] 1.57Å' scene=''>
-	~~Authors~~: ~~Harijan, R~~.K., ~~Ducati~~, R.G., ~~Namanja~~-~~Magliano~~, H.A., ~~Bonanno~~, J.B., ~~Almo, S~~.C., ~~Schramm, V~~.L.	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[6aqs]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6AQS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6AQS FirstGlance]. <br>
-	~~Description: Crystal structure of Plasmodium falciparum purine nucleoside phosphorylase (V181D) mutant complexed with DADMe-ImmG and phosphate~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=IM5:2-AMINO-7-{[(3R,4R)-3-HYDROXY-4-(HYDROXYMETHYL)PYRROLIDIN-1-YL]METHYL}-3,5-DIHYDRO-4H-PYRROLO[3,2-D]PYRIMIDIN-4-ONE'>IM5</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr>
-	[[Category: ~~Unreleased Structures~~]]	+	<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>
-	[[Category: Almo, S.C]]	+	<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=6aqs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6aqs OCA], [http://pdbe.org/6aqs PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6aqs RCSB], [http://www.ebi.ac.uk/pdbsum/6aqs PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6aqs ProSAT]</span></td></tr>
-	[[Category: ~~Schramm~~, ~~V.L~~]]	+	</table>
-	[[Category: Harijan, R.K]]	+	__TOC__
-	[[Category: Namanja-Magliano, H.A]]	+	</StructureSection>
-	[[Category: ~~Bonanno~~, ~~J.B~~]]	+	[[Category: Purine-nucleoside phosphorylase]]
-	[[Category: ~~Ducati, R.G~~]]	+	[[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: Dadme-immg]]
		+	[[Category: Phosphorylase]]
		+	[[Category: Plasmodium falciparum]]
		+	[[Category: Pnp mutant]]
		+	[[Category: Transferase]]

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

OCA — Wed, 27 Sep 2017 16:41:33 GMT

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

←Older revision

Revision as of 16:41, 27 September 2017

OCA: New page: '''Unreleased structure''' The entry 6aqs 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 16:41:32 GMT

New page: '''Unreleased structure''' The entry 6aqs 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 6aqs 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 (V181D) mutant complexed with DADMe-ImmG and phosphate
[[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]]