4ncx - Revision history

OCA at 16:53, 20 September 2023

2023-09-20T16:53:57Z

←Older revision		Revision as of 16:53, 20 September 2023
Line 1:		Line 1:

	==Crystal Structure of Prolyl-tRNA synthetase (ProRS, Proline--tRNA ligase) from Plasmodium falciparum 3D7==		==Crystal Structure of Prolyl-tRNA synthetase (ProRS, Proline--tRNA ligase) from Plasmodium falciparum 3D7==
-	<StructureSection load='4ncx' size='340' side='right'caption='[[4ncx]]' scene=''>	+	<StructureSection load='4ncx' size='340' side='right'caption='[[4ncx]], [[Resolution\|resolution]] 1.85Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4NCX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4NCX FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4ncx]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Plasmodium_falciparum_3D7 Plasmodium falciparum 3D7]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4NCX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4NCX FirstGlance]. <br>
-	</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=4ncx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ncx OCA], [https://pdbe.org/4ncx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ncx RCSB], [https://www.ebi.ac.uk/pdbsum/4ncx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ncx ProSAT]</span></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]] 1.85Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</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=4ncx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ncx OCA], [https://pdbe.org/4ncx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ncx RCSB], [https://www.ebi.ac.uk/pdbsum/4ncx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ncx ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/SYP_PLAF7 SYP_PLAF7] Catalyzes the attachment of proline to tRNA(Pro) in a two-step reaction: proline is first activated by ATP to form Pro-AMP and then transferred to the acceptor end of tRNA(Pro) (By similarity). Functions in trans to edit the amino acid moiety from incorrectly charged Ala-tRNA(Pro). Has no activity on correctly charged Pro-tRNA(Pro) or Ala-tRNA(Ala).<ref>PMID:14663147</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Plasmodium falciparum (Pf) prolyl-tRNA synthetase (ProRS) is one of the few chemical-genetically validated drug targets for malaria, yet highly selective inhibitors have not been described. In this paper, approximately 40,000 compounds were screened to identify compounds that selectively inhibit PfProRS enzyme activity vs. H. sapiens (Hs) ProRS. X-ray crystallography structures were solved for apo, as well as substrate, and inhibitor bound forms of PfProRS. We identified two new inhibitors of PfProRS that bind outside the active site. These two allosteric inhibitors showed >100X specificity for PfProRS compared to HsProRS, demonstrating this class of compounds could overcome the toxicity related to HsProRS inhibition by halofuginone and its analogs. Initial medicinal chemistry was performed on one of the two compounds, guided by the co-crystallography of the compound with PfProRS, and the results can instruct future medicinal chemistry work to optimize these promising new leads for drug development against malaria.
		+
		+	Biochemical and Structural Characterization of Selective Allosteric Inhibitors of the Plasmodium falciparum Drug Target, Prolyl-tRNA-synthetase.,Nakazawa Hewitt S, Dranow DM, Horst BG, Abendroth JA, Forte B, Hallyburton I, Jansen C, Baragana B, Choi R, Rivas KL, Hulverson MA, Dumais M, Edwards TE, Lorimer DD, Fairlamb AH, Gray DW, Read KD, Lehane AM, Kirk K, Myler PJ, Wernimont A, Walpole CS, Stacy R, Barrett LK, Gilbert IH, Van Voorhis WC ACS Infect Dis. 2016 Oct 31. PMID:27798837<ref>PMID:27798837</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 4ncx" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
	*[[Aminoacyl tRNA synthetase 3D structures\|Aminoacyl tRNA synthetase 3D structures]]		*[[Aminoacyl tRNA synthetase 3D structures\|Aminoacyl tRNA synthetase 3D structures]]
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
		+	[[Category: Plasmodium falciparum 3D7]]
	[[Category: Structural genomic]]		[[Category: Structural genomic]]

OCA at 10:49, 31 August 2022

2022-08-31T10:49:22Z

←Older revision		Revision as of 10:49, 31 August 2022
Line 1:		Line 1:

	==Crystal Structure of Prolyl-tRNA synthetase (ProRS, Proline--tRNA ligase) from Plasmodium falciparum 3D7==		==Crystal Structure of Prolyl-tRNA synthetase (ProRS, Proline--tRNA ligase) from Plasmodium falciparum 3D7==
-	<StructureSection load='4ncx' size='340' side='right'caption='[[4ncx]]~~, [[Resolution\|resolution]] 1.85Å~~' scene=''>	+	<StructureSection load='4ncx' size='340' side='right'caption='[[4ncx]]' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>~~[[4ncx]] is a 2 chain structure.~~ Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4NCX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4NCX FirstGlance]. <br>	+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4NCX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4NCX FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene></td></tr>	+	</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=4ncx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ncx OCA], [https://pdbe.org/4ncx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ncx RCSB], [https://www.ebi.ac.uk/pdbsum/4ncx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ncx ProSAT]</span></td></tr>
-	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Proline--tRNA_ligase Proline--tRNA ligase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=6.1.1.15 6.1.1.15] </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=4ncx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ncx OCA], [https://pdbe.org/4ncx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ncx RCSB], [https://www.ebi.ac.uk/pdbsum/4ncx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ncx ProSAT]</span></td></tr>	+
	</table>		</table>
-	== Function ==
-	[[https://www.uniprot.org/uniprot/SYP_PLAF7 SYP_PLAF7]] Catalyzes the attachment of proline to tRNA(Pro) in a two-step reaction: proline is first activated by ATP to form Pro-AMP and then transferred to the acceptor end of tRNA(Pro) (By similarity). Functions in trans to edit the amino acid moiety from incorrectly charged Ala-tRNA(Pro). Has no activity on correctly charged Pro-tRNA(Pro) or Ala-tRNA(Ala).<ref>PMID:14663147</ref>
-	<div style="background-color:#fffaf0;">
-	== Publication Abstract from PubMed ==
-	Plasmodium falciparum (Pf) prolyl-tRNA synthetase (ProRS) is one of the few chemical-genetically validated drug targets for malaria, yet highly selective inhibitors have not been described. In this paper, approximately 40,000 compounds were screened to identify compounds that selectively inhibit PfProRS enzyme activity vs. H. sapiens (Hs) ProRS. X-ray crystallography structures were solved for apo, as well as substrate, and inhibitor bound forms of PfProRS. We identified two new inhibitors of PfProRS that bind outside the active site. These two allosteric inhibitors showed >100X specificity for PfProRS compared to HsProRS, demonstrating this class of compounds could overcome the toxicity related to HsProRS inhibition by halofuginone and its analogs. Initial medicinal chemistry was performed on one of the two compounds, guided by the co-crystallography of the compound with PfProRS, and the results can instruct future medicinal chemistry work to optimize these promising new leads for drug development against malaria.
-
-	Biochemical and Structural Characterization of Selective Allosteric Inhibitors of the Plasmodium falciparum Drug Target, Prolyl-tRNA-synthetase.,Nakazawa Hewitt S, Dranow DM, Horst BG, Abendroth JA, Forte B, Hallyburton I, Jansen C, Baragana B, Choi R, Rivas KL, Hulverson MA, Dumais M, Edwards TE, Lorimer DD, Fairlamb AH, Gray DW, Read KD, Lehane AM, Kirk K, Myler PJ, Wernimont A, Walpole CS, Stacy R, Barrett LK, Gilbert IH, Van Voorhis WC ACS Infect Dis. 2016 Oct 31. PMID:27798837<ref>PMID:27798837</ref>
-
-	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	</div>
-	<div class="pdbe-citations 4ncx" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
	*[[Aminoacyl tRNA synthetase 3D structures\|Aminoacyl tRNA synthetase 3D structures]]		*[[Aminoacyl tRNA synthetase 3D structures\|Aminoacyl tRNA synthetase 3D structures]]
-	== References ==
-	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Proline--tRNA ligase]]
	[[Category: Structural genomic]]		[[Category: Structural genomic]]
-	[[Category: Ligase]]
-	[[Category: National institute of allergy and infectious disease]]
-	[[Category: Niaid]]
-	[[Category: Prolyl-trna synthetase]]
-	[[Category: Ssgcid]]

OCA at 05:04, 25 August 2022

2022-08-25T05:04:51Z

←Older revision		Revision as of 05:04, 25 August 2022
Line 1:		Line 1:

	==Crystal Structure of Prolyl-tRNA synthetase (ProRS, Proline--tRNA ligase) from Plasmodium falciparum 3D7==		==Crystal Structure of Prolyl-tRNA synthetase (ProRS, Proline--tRNA ligase) from Plasmodium falciparum 3D7==
-	<StructureSection load='4ncx' size='340' side='right' caption='[[4ncx]], [[Resolution\|resolution]] 1.85Å' scene=''>	+	<StructureSection load='4ncx' size='340' side='right'caption='[[4ncx]], [[Resolution\|resolution]] 1.85Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4ncx]] is a 2 chain structure ~~with sequence from [http://en.wikipedia.org/wiki/Plaf7 Plaf7]~~. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4NCX OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4NCX FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4ncx]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4NCX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4NCX FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>~~</td></tr>~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene></td></tr>
-	~~<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">proRS, PFL0670c ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=36329 PLAF7])~~</td></tr>	+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Proline--tRNA_ligase Proline--tRNA ligase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=6.1.1.15 6.1.1.15] </span></td></tr>
-	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://en.wikipedia.org/wiki/Proline--tRNA_ligase Proline--tRNA ligase], with EC number [~~http~~://www.brenda-enzymes.info/php/result_flat.php4?ecno=6.1.1.15 6.1.1.15] </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=4ncx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ncx OCA], [https://pdbe.org/4ncx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ncx RCSB], [https://www.ebi.ac.uk/pdbsum/4ncx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ncx 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=4ncx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ncx OCA], [~~http~~://pdbe.org/4ncx PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4ncx RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4ncx PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4ncx ProSAT]</span></td></tr>	+
	</table>		</table>
	== Function ==		== Function ==
-	[[~~http~~://www.uniprot.org/uniprot/SYP_PLAF7 SYP_PLAF7]] Catalyzes the attachment of proline to tRNA(Pro) in a two-step reaction: proline is first activated by ATP to form Pro-AMP and then transferred to the acceptor end of tRNA(Pro) (By similarity). Functions in trans to edit the amino acid moiety from incorrectly charged Ala-tRNA(Pro). Has no activity on correctly charged Pro-tRNA(Pro) or Ala-tRNA(Ala).<ref>PMID:14663147</ref>	+	[[https://www.uniprot.org/uniprot/SYP_PLAF7 SYP_PLAF7]] Catalyzes the attachment of proline to tRNA(Pro) in a two-step reaction: proline is first activated by ATP to form Pro-AMP and then transferred to the acceptor end of tRNA(Pro) (By similarity). Functions in trans to edit the amino acid moiety from incorrectly charged Ala-tRNA(Pro). Has no activity on correctly charged Pro-tRNA(Pro) or Ala-tRNA(Ala).<ref>PMID:14663147</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 20:		Line 19:
	</div>		</div>
	<div class="pdbe-citations 4ncx" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 4ncx" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Aminoacyl tRNA synthetase 3D structures\|Aminoacyl tRNA synthetase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Plaf7~~]]	+	[[Category: Large Structures]]
	[[Category: Proline--tRNA ligase]]		[[Category: Proline--tRNA ligase]]
	[[Category: Structural genomic]]		[[Category: Structural genomic]]

OCA at 10:04, 15 November 2017

2017-11-15T10:04:23Z

←Older revision		Revision as of 10:04, 15 November 2017
Line 3:		Line 3:
	<StructureSection load='4ncx' size='340' side='right' caption='[[4ncx]], [[Resolution\|resolution]] 1.85Å' scene=''>		<StructureSection load='4ncx' size='340' side='right' caption='[[4ncx]], [[Resolution\|resolution]] 1.85Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4ncx]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4NCX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4NCX FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4ncx]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Plaf7 Plaf7]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4NCX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4NCX FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">proRS, PFL0670c ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=36329 PLAF7])</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Proline--tRNA_ligase Proline--tRNA ligase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=6.1.1.15 6.1.1.15] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Proline--tRNA_ligase Proline--tRNA ligase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=6.1.1.15 6.1.1.15] </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=4ncx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ncx OCA], [http://pdbe.org/4ncx PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4ncx RCSB], [http://www.ebi.ac.uk/pdbsum/4ncx PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4ncx 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=4ncx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ncx OCA], [http://pdbe.org/4ncx PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4ncx RCSB], [http://www.ebi.ac.uk/pdbsum/4ncx PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4ncx ProSAT]</span></td></tr>
Line 23:		Line 24:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Plaf7]]
	[[Category: Proline--tRNA ligase]]		[[Category: Proline--tRNA ligase]]
	[[Category: Structural genomic]]		[[Category: Structural genomic]]

OCA at 03:34, 10 December 2016

2016-12-10T03:34:29Z

←Older revision		Revision as of 03:34, 10 December 2016
Line 10:		Line 10:
	== Function ==		== Function ==
	[[http://www.uniprot.org/uniprot/SYP_PLAF7 SYP_PLAF7]] Catalyzes the attachment of proline to tRNA(Pro) in a two-step reaction: proline is first activated by ATP to form Pro-AMP and then transferred to the acceptor end of tRNA(Pro) (By similarity). Functions in trans to edit the amino acid moiety from incorrectly charged Ala-tRNA(Pro). Has no activity on correctly charged Pro-tRNA(Pro) or Ala-tRNA(Ala).<ref>PMID:14663147</ref>		[[http://www.uniprot.org/uniprot/SYP_PLAF7 SYP_PLAF7]] Catalyzes the attachment of proline to tRNA(Pro) in a two-step reaction: proline is first activated by ATP to form Pro-AMP and then transferred to the acceptor end of tRNA(Pro) (By similarity). Functions in trans to edit the amino acid moiety from incorrectly charged Ala-tRNA(Pro). Has no activity on correctly charged Pro-tRNA(Pro) or Ala-tRNA(Ala).<ref>PMID:14663147</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Plasmodium falciparum (Pf) prolyl-tRNA synthetase (ProRS) is one of the few chemical-genetically validated drug targets for malaria, yet highly selective inhibitors have not been described. In this paper, approximately 40,000 compounds were screened to identify compounds that selectively inhibit PfProRS enzyme activity vs. H. sapiens (Hs) ProRS. X-ray crystallography structures were solved for apo, as well as substrate, and inhibitor bound forms of PfProRS. We identified two new inhibitors of PfProRS that bind outside the active site. These two allosteric inhibitors showed >100X specificity for PfProRS compared to HsProRS, demonstrating this class of compounds could overcome the toxicity related to HsProRS inhibition by halofuginone and its analogs. Initial medicinal chemistry was performed on one of the two compounds, guided by the co-crystallography of the compound with PfProRS, and the results can instruct future medicinal chemistry work to optimize these promising new leads for drug development against malaria.
		+
		+	Biochemical and Structural Characterization of Selective Allosteric Inhibitors of the Plasmodium falciparum Drug Target, Prolyl-tRNA-synthetase.,Nakazawa Hewitt S, Dranow DM, Horst BG, Abendroth JA, Forte B, Hallyburton I, Jansen C, Baragana B, Choi R, Rivas KL, Hulverson MA, Dumais M, Edwards TE, Lorimer DD, Fairlamb AH, Gray DW, Read KD, Lehane AM, Kirk K, Myler PJ, Wernimont A, Walpole CS, Stacy R, Barrett LK, Gilbert IH, Van Voorhis WC ACS Infect Dis. 2016 Oct 31. PMID:27798837<ref>PMID:27798837</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 4ncx" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>

OCA at 22:16, 5 August 2016

2016-08-05T22:16:41Z

←Older revision		Revision as of 22:16, 5 August 2016
Line 1:		Line 1:
		+
	==Crystal Structure of Prolyl-tRNA synthetase (ProRS, Proline--tRNA ligase) from Plasmodium falciparum 3D7==		==Crystal Structure of Prolyl-tRNA synthetase (ProRS, Proline--tRNA ligase) from Plasmodium falciparum 3D7==
	<StructureSection load='4ncx' size='340' side='right' caption='[[4ncx]], [[Resolution\|resolution]] 1.85Å' scene=''>		<StructureSection load='4ncx' size='340' side='right' caption='[[4ncx]], [[Resolution\|resolution]] 1.85Å' scene=''>
Line 5:		Line 6:
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene></td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Proline--tRNA_ligase Proline--tRNA ligase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=6.1.1.15 6.1.1.15] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Proline--tRNA_ligase Proline--tRNA ligase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=6.1.1.15 6.1.1.15] </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=4ncx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ncx OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4ncx RCSB], [http://www.ebi.ac.uk/pdbsum/4ncx PDBsum]</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=4ncx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ncx OCA], [http://pdbe.org/4ncx PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4ncx RCSB], [http://www.ebi.ac.uk/pdbsum/4ncx PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4ncx ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==

OCA at 06:19, 25 December 2014

2014-12-25T06:19:12Z

←Older revision		Revision as of 06:19, 25 December 2014
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	<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=4ncx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ncx OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4ncx RCSB], [http://www.ebi.ac.uk/pdbsum/4ncx PDBsum]</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=4ncx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ncx OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4ncx RCSB], [http://www.ebi.ac.uk/pdbsum/4ncx PDBsum]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/SYP_PLAF7 SYP_PLAF7]] Catalyzes the attachment of proline to tRNA(Pro) in a two-step reaction: proline is first activated by ATP to form Pro-AMP and then transferred to the acceptor end of tRNA(Pro) (By similarity). Functions in trans to edit the amino acid moiety from incorrectly charged Ala-tRNA(Pro). Has no activity on correctly charged Pro-tRNA(Pro) or Ala-tRNA(Ala).<ref>PMID:14663147</ref>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: Proline--tRNA ligase]]		[[Category: Proline--tRNA ligase]]
-	[[Category: ~~Disease, Seattle~~ Structural ~~Genomics Center for Infectious.~~]]	+	[[Category: Structural genomic]]
	[[Category: Ligase]]		[[Category: Ligase]]
	[[Category: National institute of allergy and infectious disease]]		[[Category: National institute of allergy and infectious disease]]
	[[Category: Niaid]]		[[Category: Niaid]]
	[[Category: Prolyl-trna synthetase]]		[[Category: Prolyl-trna synthetase]]
-	[[Category: Seattle structural genomics center for infectious disease]]
	[[Category: Ssgcid]]		[[Category: Ssgcid]]
-	[[Category: Structural genomic]]

OCA at 11:26, 29 October 2014

2014-10-29T11:26:36Z

←Older revision		Revision as of 11:26, 29 October 2014
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-	'''~~Unreleased structure~~'''	+	==Crystal Structure of Prolyl-tRNA synthetase (ProRS, Proline--tRNA ligase) from Plasmodium falciparum 3D7==
-		+	<StructureSection load='4ncx' size='340' side='right' caption='[[4ncx]], [[Resolution\|resolution]] 1.85Å' scene=''>
-	~~The entry~~ 4ncx is ~~ON HOLD until Oct 23 2015~~	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[4ncx]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4NCX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4NCX FirstGlance]. <br>
-	~~Authors~~: Seattle Structural Genomics Center for Infectious ~~Disease~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene></td></tr>
-		+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Proline--tRNA_ligase Proline--tRNA ligase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=6.1.1.15 6.1.1.15] </span></td></tr>
-	~~Description~~: ~~Crystal Structure~~ of Prolyl-~~tRNA~~ synthetase ~~(ProRS, Proline--tRNA ligase) from Plasmodium falciparum 3D7~~	+	<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=4ncx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ncx OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4ncx RCSB], [http://www.ebi.ac.uk/pdbsum/4ncx PDBsum]</span></td></tr>
		+	</table>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Proline--tRNA ligase]]
		+	[[Category: Disease, Seattle Structural Genomics Center for Infectious.]]
		+	[[Category: Ligase]]
		+	[[Category: National institute of allergy and infectious disease]]
		+	[[Category: Niaid]]
		+	[[Category: Prolyl-trna synthetase]]
		+	[[Category: Seattle structural genomics center for infectious disease]]
		+	[[Category: Ssgcid]]
		+	[[Category: Structural genomic]]

OCA at 06:09, 8 October 2014

2014-10-08T06:09:44Z

←Older revision		Revision as of 06:09, 8 October 2014
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 4ncx is ON HOLD until ~~Paper Publication~~	+	The entry 4ncx is ON HOLD until Oct 23 2015

	Authors: Seattle Structural Genomics Center for Infectious Disease		Authors: Seattle Structural Genomics Center for Infectious Disease

	Description: Crystal Structure of Prolyl-tRNA synthetase (ProRS, Proline--tRNA ligase) from Plasmodium falciparum 3D7		Description: Crystal Structure of Prolyl-tRNA synthetase (ProRS, Proline--tRNA ligase) from Plasmodium falciparum 3D7

OCA: Protected "4ncx" [edit=sysop:move=sysop]

2013-11-13T07:43:34Z

Protected "4ncx" [edit=sysop:move=sysop]

←Older revision

Revision as of 07:43, 13 November 2013