4hvc - Revision history

OCA at 11:44, 1 March 2024

OCA — Fri, 01 Mar 2024 11:44:59 GMT

←Older revision		Revision as of 11:44, 1 March 2024
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4hvc]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4HVC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4HVC FirstGlance]. <br>		<table><tr><td colspan='2'>[[4hvc]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4HVC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4HVC FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ANP:PHOSPHOAMINOPHOSPHONIC+ACID-ADENYLATE+ESTER'>ANP</scene>, <scene name='pdbligand=HFG:7-BROMO-6-CHLORO-3-{3-[(2R,3S)-3-HYDROXYPIPERIDIN-2-YL]-2-OXOPROPYL}QUINAZOLIN-4(3H)-ONE'>HFG</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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]] 2Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ANP:PHOSPHOAMINOPHOSPHONIC+ACID-ADENYLATE+ESTER'>ANP</scene>, <scene name='pdbligand=HFG:7-BROMO-6-CHLORO-3-{3-[(2R,3S)-3-HYDROXYPIPERIDIN-2-YL]-2-OXOPROPYL}QUINAZOLIN-4(3H)-ONE'>HFG</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=4hvc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4hvc OCA], [https://pdbe.org/4hvc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4hvc RCSB], [https://www.ebi.ac.uk/pdbsum/4hvc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4hvc 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=4hvc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4hvc OCA], [https://pdbe.org/4hvc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4hvc RCSB], [https://www.ebi.ac.uk/pdbsum/4hvc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4hvc ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
	[https://www.uniprot.org/uniprot/SYEP_HUMAN SYEP_HUMAN] Catalyzes the attachment of the cognate amino acid to the corresponding tRNA in a two-step reaction: the amino acid is first activated by ATP to form a covalent intermediate with AMP and is then transferred to the acceptor end of the cognate tRNA. Component of the GAIT (gamma interferon-activated inhibitor of translation) complex which mediates interferon-gamma-induced transcript-selective translation inhibition in inflammation processes. Upon interferon-gamma activation and subsequent phosphorylation dissociates from the multisynthetase complex and assembles into the GAIT complex which binds to stem loop-containing GAIT elements in the 3'-UTR of diverse inflammatory mRNAs (such as ceruplasmin) and suppresses their translation.<ref>PMID:1756734</ref> <ref>PMID:15479637</ref> <ref>PMID:23071094</ref>		[https://www.uniprot.org/uniprot/SYEP_HUMAN SYEP_HUMAN] Catalyzes the attachment of the cognate amino acid to the corresponding tRNA in a two-step reaction: the amino acid is first activated by ATP to form a covalent intermediate with AMP and is then transferred to the acceptor end of the cognate tRNA. Component of the GAIT (gamma interferon-activated inhibitor of translation) complex which mediates interferon-gamma-induced transcript-selective translation inhibition in inflammation processes. Upon interferon-gamma activation and subsequent phosphorylation dissociates from the multisynthetase complex and assembles into the GAIT complex which binds to stem loop-containing GAIT elements in the 3'-UTR of diverse inflammatory mRNAs (such as ceruplasmin) and suppresses their translation.<ref>PMID:1756734</ref> <ref>PMID:15479637</ref> <ref>PMID:23071094</ref>
-	<div style="background-color:#fffaf0;">
-	== Publication Abstract from PubMed ==
-	Febrifugine is the active component of the Chinese herb Chang Shan (Dichroa febrifuga Lour.), which has been used for treating malaria-induced fever for about 2,000 years. Halofuginone (HF), the halogenated derivative of febrifugine, has been tested in clinical trials for potential therapeutic applications in cancer and fibrotic disease. Recently, HF was reported to inhibit T(H)17 cell differentiation by activating the amino acid response pathway, through inhibiting human prolyl-transfer RNA synthetase (ProRS) to cause intracellular accumulation of uncharged tRNA. Curiously, inhibition requires the presence of unhydrolysed ATP. Here we report an unusual 2.0 A structure showing that ATP directly locks onto and orients two parts of HF onto human ProRS, so that one part of HF mimics bound proline and the other mimics the 3' end of bound tRNA. Thus, HF is a new type of ATP-dependent inhibitor that simultaneously occupies two different substrate binding sites on ProRS. Moreover, our structure indicates a possible similar mechanism of action for febrifugine in malaria treatment. Finally, the elucidation here of a two-site modular targeting activity of HF raises the possibility that substrate-directed capture of similar inhibitors might be a general mechanism that could be applied to other synthetases.
-
-	ATP-directed capture of bioactive herbal-based medicine on human tRNA synthetase.,Zhou H, Sun L, Yang XL, Schimmel P Nature. 2012 Dec 23. doi: 10.1038/nature11774. PMID:23263184<ref>PMID:23263184</ref>
-
-	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	</div>
-	<div class="pdbe-citations 4hvc" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==

OCA at 08:18, 9 November 2022

OCA — Wed, 09 Nov 2022 08:18:09 GMT

←Older revision		Revision as of 08:18, 9 November 2022
Line 1:		Line 1:

	==Crystal structure of human prolyl-tRNA synthetase in complex with halofuginone and ATP analogue==		==Crystal structure of human prolyl-tRNA synthetase in complex with halofuginone and ATP analogue==
-	<StructureSection load='4hvc' size='340' side='right' caption='[[4hvc]], [[Resolution\|resolution]] 2.00Å' scene=''>	+	<StructureSection load='4hvc' size='340' side='right'caption='[[4hvc]], [[Resolution\|resolution]] 2.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4hvc]] is a 2 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~Human Human~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4HVC OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4HVC FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4hvc]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4HVC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4HVC FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ANP:PHOSPHOAMINOPHOSPHONIC+ACID-ADENYLATE+ESTER'>ANP</scene>, <scene name='pdbligand=HFG:7-BROMO-6-CHLORO-3-{3-[(2R,3S)-3-HYDROXYPIPERIDIN-2-YL]-2-OXOPROPYL}QUINAZOLIN-4(3H)-ONE'>HFG</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene>~~</td></tr>~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ANP:PHOSPHOAMINOPHOSPHONIC+ACID-ADENYLATE+ESTER'>ANP</scene>, <scene name='pdbligand=HFG:7-BROMO-6-CHLORO-3-{3-[(2R,3S)-3-HYDROXYPIPERIDIN-2-YL]-2-OXOPROPYL}QUINAZOLIN-4(3H)-ONE'>HFG</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">EPRS, GLNS, PARS, QARS, QPRS, PIG32 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=4hvc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4hvc OCA], [https://pdbe.org/4hvc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4hvc RCSB], [https://www.ebi.ac.uk/pdbsum/4hvc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4hvc 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=4hvc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4hvc OCA], [~~http~~://pdbe.org/4hvc PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4hvc RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4hvc PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4hvc ProSAT]</span></td></tr>	+
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/SYEP_HUMAN SYEP_HUMAN]] Catalyzes the attachment of the cognate amino acid to the corresponding tRNA in a two-step reaction: the amino acid is first activated by ATP to form a covalent intermediate with AMP and is then transferred to the acceptor end of the cognate tRNA. Component of the GAIT (gamma interferon-activated inhibitor of translation) complex which mediates interferon-gamma-induced transcript-selective translation inhibition in inflammation processes. Upon interferon-gamma activation and subsequent phosphorylation dissociates from the multisynthetase complex and assembles into the GAIT complex which binds to stem loop-containing GAIT elements in the 3'-UTR of diverse inflammatory mRNAs (such as ceruplasmin) and suppresses their translation.<ref>PMID:1756734</ref> <ref>PMID:15479637</ref> <ref>PMID:23071094</ref>	+	[https://www.uniprot.org/uniprot/SYEP_HUMAN SYEP_HUMAN] Catalyzes the attachment of the cognate amino acid to the corresponding tRNA in a two-step reaction: the amino acid is first activated by ATP to form a covalent intermediate with AMP and is then transferred to the acceptor end of the cognate tRNA. Component of the GAIT (gamma interferon-activated inhibitor of translation) complex which mediates interferon-gamma-induced transcript-selective translation inhibition in inflammation processes. Upon interferon-gamma activation and subsequent phosphorylation dissociates from the multisynthetase complex and assembles into the GAIT complex which binds to stem loop-containing GAIT elements in the 3'-UTR of diverse inflammatory mRNAs (such as ceruplasmin) and suppresses their translation.<ref>PMID:1756734</ref> <ref>PMID:15479637</ref> <ref>PMID:23071094</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 19:		Line 18:
	</div>		</div>
	<div class="pdbe-citations 4hvc" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 4hvc" 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: ~~Human~~]]	+	[[Category: Homo sapiens]]
-	[[Category: ~~Schimmel, P~~]]	+	[[Category: Large Structures]]
-	[[Category: ~~Sun, L~~]]	+	[[Category: Schimmel P]]
-	[[Category: ~~Yang, X~~ L]]	+	[[Category: Sun L]]
-	[[Category: ~~Zhou, H~~]]	+	[[Category: Yang XL]]
-	[[Category: ~~Ligase]]~~	+	[[Category: Zhou H]]
-	~~[[Category: Ligase-ligase inhibitor complex~~]]	+

OCA at 14:53, 4 August 2016

OCA — Thu, 04 Aug 2016 14:53:04 GMT

←Older revision		Revision as of 14:53, 4 August 2016
Line 1:		Line 1:
		+
	==Crystal structure of human prolyl-tRNA synthetase in complex with halofuginone and ATP analogue==		==Crystal structure of human prolyl-tRNA synthetase in complex with halofuginone and ATP analogue==
	<StructureSection load='4hvc' size='340' side='right' caption='[[4hvc]], [[Resolution\|resolution]] 2.00Å' scene=''>		<StructureSection load='4hvc' size='340' side='right' caption='[[4hvc]], [[Resolution\|resolution]] 2.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4hvc]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/~~Homo_sapiens Homo sapiens~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4HVC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4HVC FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4hvc]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4HVC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4HVC FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ANP:PHOSPHOAMINOPHOSPHONIC+ACID-ADENYLATE+ESTER'>ANP</scene>, <scene name='pdbligand=HFG:7-BROMO-6-CHLORO-3-{3-[(2R,3S)-3-HYDROXYPIPERIDIN-2-YL]-2-OXOPROPYL}QUINAZOLIN-4(3H)-ONE'>HFG</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ANP:PHOSPHOAMINOPHOSPHONIC+ACID-ADENYLATE+ESTER'>ANP</scene>, <scene name='pdbligand=HFG:7-BROMO-6-CHLORO-3-{3-[(2R,3S)-3-HYDROXYPIPERIDIN-2-YL]-2-OXOPROPYL}QUINAZOLIN-4(3H)-ONE'>HFG</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">EPRS, GLNS, PARS, QARS, QPRS, PIG32 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 ~~Homo sapiens~~])</td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">EPRS, GLNS, PARS, QARS, QPRS, PIG32 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=4hvc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4hvc OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4hvc RCSB], [http://www.ebi.ac.uk/pdbsum/4hvc 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=4hvc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4hvc OCA], [http://pdbe.org/4hvc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4hvc RCSB], [http://www.ebi.ac.uk/pdbsum/4hvc PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4hvc ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 17:		Line 18:
	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	</div>		</div>
		+	<div class="pdbe-citations 4hvc" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Homo sapiens~~]]	+	[[Category: Human]]
	[[Category: Schimmel, P]]		[[Category: Schimmel, P]]
	[[Category: Sun, L]]		[[Category: Sun, L]]

OCA at 10:16, 25 December 2014

OCA — Thu, 25 Dec 2014 10:16:51 GMT

←Older revision		Revision as of 10:16, 25 December 2014
Line 7:		Line 7:
	<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=4hvc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4hvc OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4hvc RCSB], [http://www.ebi.ac.uk/pdbsum/4hvc 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=4hvc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4hvc OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4hvc RCSB], [http://www.ebi.ac.uk/pdbsum/4hvc PDBsum]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/SYEP_HUMAN SYEP_HUMAN]] Catalyzes the attachment of the cognate amino acid to the corresponding tRNA in a two-step reaction: the amino acid is first activated by ATP to form a covalent intermediate with AMP and is then transferred to the acceptor end of the cognate tRNA. Component of the GAIT (gamma interferon-activated inhibitor of translation) complex which mediates interferon-gamma-induced transcript-selective translation inhibition in inflammation processes. Upon interferon-gamma activation and subsequent phosphorylation dissociates from the multisynthetase complex and assembles into the GAIT complex which binds to stem loop-containing GAIT elements in the 3'-UTR of diverse inflammatory mRNAs (such as ceruplasmin) and suppresses their translation.<ref>PMID:1756734</ref> <ref>PMID:15479637</ref> <ref>PMID:23071094</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==

OCA at 16:58, 10 December 2014

OCA — Wed, 10 Dec 2014 16:58:49 GMT

←Older revision		Revision as of 16:58, 10 December 2014
Line 1:		Line 1:
-	[[~~Image:~~4hvc.~~png~~\|~~left~~\|~~200px~~]]	+	==Crystal structure of human prolyl-tRNA synthetase in complex with halofuginone and ATP analogue==
		+	<StructureSection load='4hvc' size='340' side='right' caption='[[4hvc]], [[Resolution\|resolution]] 2.00Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[4hvc]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4HVC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4HVC FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ANP:PHOSPHOAMINOPHOSPHONIC+ACID-ADENYLATE+ESTER'>ANP</scene>, <scene name='pdbligand=HFG:7-BROMO-6-CHLORO-3-{3-[(2R,3S)-3-HYDROXYPIPERIDIN-2-YL]-2-OXOPROPYL}QUINAZOLIN-4(3H)-ONE'>HFG</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">EPRS, GLNS, PARS, QARS, QPRS, PIG32 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</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=4hvc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4hvc OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4hvc RCSB], [http://www.ebi.ac.uk/pdbsum/4hvc PDBsum]</span></td></tr>
		+	</table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Febrifugine is the active component of the Chinese herb Chang Shan (Dichroa febrifuga Lour.), which has been used for treating malaria-induced fever for about 2,000 years. Halofuginone (HF), the halogenated derivative of febrifugine, has been tested in clinical trials for potential therapeutic applications in cancer and fibrotic disease. Recently, HF was reported to inhibit T(H)17 cell differentiation by activating the amino acid response pathway, through inhibiting human prolyl-transfer RNA synthetase (ProRS) to cause intracellular accumulation of uncharged tRNA. Curiously, inhibition requires the presence of unhydrolysed ATP. Here we report an unusual 2.0 A structure showing that ATP directly locks onto and orients two parts of HF onto human ProRS, so that one part of HF mimics bound proline and the other mimics the 3' end of bound tRNA. Thus, HF is a new type of ATP-dependent inhibitor that simultaneously occupies two different substrate binding sites on ProRS. Moreover, our structure indicates a possible similar mechanism of action for febrifugine in malaria treatment. Finally, the elucidation here of a two-site modular targeting activity of HF raises the possibility that substrate-directed capture of similar inhibitors might be a general mechanism that could be applied to other synthetases.

-	~~{{STRUCTURE_4hvc\| PDB=4hvc \| SCENE= }}~~	+	ATP-directed capture of bioactive herbal-based medicine on human tRNA synthetase.,Zhou H, Sun L, Yang XL, Schimmel P Nature. 2012 Dec 23. doi: 10.1038/nature11774. PMID:23263184<ref>PMID:23263184</ref>

-	~~===Crystal structure~~ of ~~human prolyl-tRNA synthetase in complex with halofuginone and ATP analogue===~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-		+	</div>
-	~~{{ABSTRACT_PUBMED_23263184}}~~	+	== References ==
-		+	<references/>
-	==~~About this Structure~~==	+	__TOC__
-	~~[[4hvc]] is a 2 chain structure with sequence from [http:~~//~~en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4HVC OCA].~~	+	</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
-	[[Category: Schimmel, P.]]	+	[[Category: Schimmel, P]]
-	[[Category: Sun, L.]]	+	[[Category: Sun, L]]
-	[[Category: Yang, X L.]]	+	[[Category: Yang, X L]]
-	[[Category: Zhou, H.]]	+	[[Category: Zhou, H]]
	[[Category: Ligase]]		[[Category: Ligase]]
	[[Category: Ligase-ligase inhibitor complex]]		[[Category: Ligase-ligase inhibitor complex]]

OCA at 09:36, 13 February 2013

OCA — Wed, 13 Feb 2013 09:36:06 GMT

←Older revision		Revision as of 09:36, 13 February 2013
Line 1:		Line 1:
-	[[Image:4hvc.~~jpg~~\|left\|200px]]	+	[[Image:4hvc.png\|left\|200px]]

	{{STRUCTURE_4hvc\| PDB=4hvc \| SCENE= }}		{{STRUCTURE_4hvc\| PDB=4hvc \| SCENE= }}

OCA at 09:23, 2 January 2013

OCA — Wed, 02 Jan 2013 09:23:48 GMT

←Older revision		Revision as of 09:23, 2 January 2013
Line 1:		Line 1:
-	~~'''Unreleased structure'''~~	+	[[Image:4hvc.jpg\|left\|200px]]

-	~~The entry~~ 4hvc ~~is ON HOLD~~ ~~until Paper Publication~~	+	{{STRUCTURE_4hvc\| PDB=4hvc \| SCENE= }}

-	~~Authors: Zhou, H., Sun, L., Yang, X.L., Schimmel, P.~~	+	===Crystal structure of human prolyl-tRNA synthetase in complex with halofuginone and ATP analogue===

-	~~Description: Crystal~~ structure ~~of human prolyl~~-~~tRNA synthetase in~~ complex ~~with halofuginone and ATP analogue~~	+	{{ABSTRACT_PUBMED_23263184}}
		+
		+	==About this Structure==
		+	[[4hvc]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4HVC OCA].
		+	[[Category: Homo sapiens]]
		+	[[Category: Schimmel, P.]]
		+	[[Category: Sun, L.]]
		+	[[Category: Yang, X L.]]
		+	[[Category: Zhou, H.]]
		+	[[Category: Ligase]]
		+	[[Category: Ligase-ligase inhibitor complex]]

OCA at 09:07, 21 November 2012

OCA — Wed, 21 Nov 2012 09:07:39 GMT

←Older revision		Revision as of 09:07, 21 November 2012
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 4hvc is ON HOLD	+	The entry 4hvc is ON HOLD until Paper Publication

	Authors: Zhou, H., Sun, L., Yang, X.L., Schimmel, P.		Authors: Zhou, H., Sun, L., Yang, X.L., Schimmel, P.

	Description: Crystal structure of human prolyl-tRNA synthetase in complex with halofuginone and ATP analogue		Description: Crystal structure of human prolyl-tRNA synthetase in complex with halofuginone and ATP analogue

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

OCA — Wed, 14 Nov 2012 06:19:57 GMT

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

←Older revision

Revision as of 06:19, 14 November 2012

OCA: New page: '''Unreleased structure''' The entry 4hvc is ON HOLD Authors: Zhou, H., Sun, L., Yang, X.L., Schimmel, P. Description: Crystal structure of human prolyl-tRNA synthetase in complex with...

OCA — Wed, 14 Nov 2012 06:19:56 GMT

New page: '''Unreleased structure''' The entry 4hvc is ON HOLD Authors: Zhou, H., Sun, L., Yang, X.L., Schimmel, P. Description: Crystal structure of human prolyl-tRNA synthetase in complex with...

New page

'''Unreleased structure'''

The entry 4hvc is ON HOLD

Authors: Zhou, H., Sun, L., Yang, X.L., Schimmel, P.

Description: Crystal structure of human prolyl-tRNA synthetase in complex with halofuginone and ATP analogue