6o76 - Revision history

OCA at 07:05, 11 October 2023

2023-10-11T07:05:39Z

←Older revision		Revision as of 07:05, 11 October 2023
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	<StructureSection load='6o76' size='340' side='right'caption='[[6o76]], [[Resolution\|resolution]] 2.79Å' scene=''>		<StructureSection load='6o76' size='340' side='right'caption='[[6o76]], [[Resolution\|resolution]] 2.79Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6o76]] 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=6O76 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6O76 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6o76]] 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=6O76 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6O76 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></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]] 2.787Å</td></tr>
-	~~<tr~~ id~~='related'><td class~~="~~sblockLbl~~">~~<b>~~[[~~Related_structure~~\|~~Related:]]</b></td><td class="sblockDat">[[4x5o\|4x5o~~]]</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></td></tr>
-	<tr id='~~gene~~'><td class="sblockLbl"><b>[[~~Gene~~\|~~Gene~~:]]</b></td><td class="sblockDat"~~>HARS, HRS ([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=6o76 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6o76 OCA], [https://pdbe.org/6o76 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6o76 RCSB], [https://www.ebi.ac.uk/pdbsum/6o76 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6o76 ProSAT]</span></td></tr>
-	~~<tr id~~='~~activity'><td class~~=~~"sblockLbl"><b>Activity~~:~~</b></td><td class="sblockDat"><span class='plainlinks~~'>~~[http://en.wikipedia.org/wiki/Histidine--tRNA_ligase Histidine--tRNA ligase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=6.1.1.21 6.1.1.21]~~ </~~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=6o76 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6o76 OCA], [~~http~~://pdbe.org/6o76 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6o76 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6o76 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6o76 ProSAT]</span></td></tr>	+
	</table>		</table>
	== Disease ==		== Disease ==
-	[~~[http~~://www.uniprot.org/uniprot/~~SYHC_HUMAN SYHC_HUMAN~~]~~] Defects in HARS are a cause of~~ Usher syndrome type ~~3B (USH3B)~~ [~~MIM:[http~~://~~omim~~.org/~~entry~~/~~614504 614504~~]~~]. USH3B is a syndrome characterized by progressive vision and hearing loss during early childhood. Some patients have~~ the so-~~called~~ '~~Charles Bonnet syndrome~~,~~' involving decreased visual acuity and vivid visual hallucinations. USH is a genetically heterogeneous condition characterized by~~ the ~~association~~ of ~~retinitis pigmentosa with sensorineural deafness. Age at onset and differences in auditory and vestibular function distinguish Usher syndrome type 1~~ (~~USH1~~)~~, Usher syndrome type 2~~ (~~USH2~~) ~~and Usher syndrome type 3~~ (~~USH3~~). USH3 is characterized by postlingual, progressive hearing loss, variable vestibular dysfunction, and onset of retinitis pigmentosa symptoms, including nyctalopia, constriction of the visual fields, and loss of central visual acuity, usually by the second decade of life.<ref>PMID:~~22279524~~</ref> Note=HARS mutations may be involved in peripheral neuropathy, a disease mainly characterized by distal motor and sensory dysfunction. Inherited peripheral neuropathies are clinically and genetically heterogeneous with variable age of onset and reduced penetrance associated with specific loci. HARS mutations may directly predispose patients to peripheral neuropathy or may modify a peripheral neuropathy phenotype by contributing to the genetic and environmental load in a given patient (PubMed:~~22930593).~~	+	[https://www.uniprot.org/uniprot/HARS1_HUMAN HARS1_HUMAN] Usher syndrome type 3;Autosomal dominant Charcot-Marie-Tooth disease type 2W. The disease is caused by variants affecting the gene represented in this entry. The disease is caused by variants affecting the gene represented in this entry.
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/HARS1_HUMAN HARS1_HUMAN] Catalyzes the ATP-dependent ligation of histidine to the 3'-end of its cognate tRNA, via the formation of an aminoacyl-adenylate intermediate (His-AMP) (PubMed:29235198). Plays a role in axon guidance (PubMed:26072516).<ref>PMID:26072516</ref> <ref>PMID:29235198</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
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	</div>		</div>
	<div class="pdbe-citations 6o76" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 6o76" 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: ~~Histidine--tRNA ligase]]~~	+	[[Category: Homo sapiens]]
-	~~[[Category: Human~~]]	+
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Kuhle, B]]	+	[[Category: Kuhle B]]
-	[[Category: Yang~~, X L]]~~	+	[[Category: Yang XL]]
-	~~[[Category: Alpha beta domain]]~~	+
-	~~[[Category: Cmt]]~~	+
-	~~[[Category: Ligase]]~~	+
-	~~[[Category: Trna]]~~	+
-	~~[[Category: Whep domain~~]]	+

OCA at 06:13, 10 October 2019

2019-10-10T06:13:30Z

←Older revision		Revision as of 06:13, 10 October 2019
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-	'''Unreleased structure'''

-	~~The entry~~ 6o76 is ~~ON HOLD~~	+	==Human cytosolic Histidyl-tRNA synthetase (HisRS) with WHEP domain==
		+	<StructureSection load='6o76' size='340' side='right'caption='[[6o76]], [[Resolution\|resolution]] 2.79Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[6o76]] 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=6O76 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6O76 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></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4x5o\|4x5o]]</td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">HARS, HRS ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
		+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Histidine--tRNA_ligase Histidine--tRNA ligase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=6.1.1.21 6.1.1.21] </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=6o76 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6o76 OCA], [http://pdbe.org/6o76 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6o76 RCSB], [http://www.ebi.ac.uk/pdbsum/6o76 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6o76 ProSAT]</span></td></tr>
		+	</table>
		+	== Disease ==
		+	[[http://www.uniprot.org/uniprot/SYHC_HUMAN SYHC_HUMAN]] Defects in HARS are a cause of Usher syndrome type 3B (USH3B) [MIM:[http://omim.org/entry/614504 614504]]. USH3B is a syndrome characterized by progressive vision and hearing loss during early childhood. Some patients have the so-called 'Charles Bonnet syndrome,' involving decreased visual acuity and vivid visual hallucinations. USH is a genetically heterogeneous condition characterized by the association of retinitis pigmentosa with sensorineural deafness. Age at onset and differences in auditory and vestibular function distinguish Usher syndrome type 1 (USH1), Usher syndrome type 2 (USH2) and Usher syndrome type 3 (USH3). USH3 is characterized by postlingual, progressive hearing loss, variable vestibular dysfunction, and onset of retinitis pigmentosa symptoms, including nyctalopia, constriction of the visual fields, and loss of central visual acuity, usually by the second decade of life.<ref>PMID:22279524</ref> Note=HARS mutations may be involved in peripheral neuropathy, a disease mainly characterized by distal motor and sensory dysfunction. Inherited peripheral neuropathies are clinically and genetically heterogeneous with variable age of onset and reduced penetrance associated with specific loci. HARS mutations may directly predispose patients to peripheral neuropathy or may modify a peripheral neuropathy phenotype by contributing to the genetic and environmental load in a given patient (PubMed:22930593).
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Aminoacyl-transfer RNA (tRNA) synthetases (aaRSs) are the largest protein family causatively linked to neurodegenerative Charcot-Marie-Tooth (CMT) disease. Dominant mutations cause the disease, and studies of CMT disease-causing mutant glycyl-tRNA synthetase (GlyRS) and tyrosyl-tRNA synthetase (TyrRS) showed their mutations create neomorphic structures consistent with a gain-of-function mechanism. In contrast, based on a haploid yeast model, loss of aminoacylation function was reported for CMT disease mutants in histidyl-tRNA synthetase (HisRS). However, neither that nor prior work of any CMT disease-causing aaRS investigated the aminoacylation status of tRNAs in the cellular milieu of actual patients. Using an assay that interrogated aminoacylation levels in patient cells, we investigated a HisRS-linked CMT disease family with the most severe disease phenotype. Strikingly, no difference in charged tRNA levels between normal and diseased family members was found. In confirmation, recombinant versions of 4 other HisRS CMT disease-causing mutants showed no correlation between activity loss in vitro and severity of phenotype in vivo. Indeed, a mutation having the most detrimental impact on activity was associated with a mild disease phenotype. In further work, using 3 independent biophysical analyses, structural opening (relaxation) of mutant HisRSs at the dimer interface best correlated with disease severity. In fact, the HisRS mutation in the severely afflicted patient family caused the largest degree of structural relaxation. These data suggest that HisRS-linked CMT disease arises from open conformation-induced mechanisms distinct from loss of aminoacylation.

-	~~Authors: Kuhle~~, B., Yang, X.L.	+	CMT disease severity correlates with mutation-induced open conformation of histidyl-tRNA synthetase, not aminoacylation loss, in patient cells.,Blocquel D, Sun L, Matuszek Z, Li S, Weber T, Kuhle B, Kooi G, Wei N, Baets J, Pan T, Schimmel P, Yang XL Proc Natl Acad Sci U S A. 2019 Sep 24;116(39):19440-19448. doi:, 10.1073/pnas.1908288116. Epub 2019 Sep 9. PMID:31501329<ref>PMID:31501329</ref>

-	~~Description~~: ~~Human cytosolic Histidyl~~-tRNA ~~synthetase (HisRS) with WHEP domain~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased Structures~~]]	+	</div>
-	[[Category: ~~Yang, X.L~~]]	+	<div class="pdbe-citations 6o76" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Histidine--tRNA ligase]]
		+	[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Kuhle, B]]		[[Category: Kuhle, B]]
		+	[[Category: Yang, X L]]
		+	[[Category: Alpha beta domain]]
		+	[[Category: Cmt]]
		+	[[Category: Ligase]]
		+	[[Category: Trna]]
		+	[[Category: Whep domain]]

OCA: Protected "6o76" [edit=sysop:move=sysop]

2019-03-13T10:18:46Z

Protected "6o76" [edit=sysop:move=sysop]

←Older revision

Revision as of 10:18, 13 March 2019

OCA: New page: '''Unreleased structure''' The entry 6o76 is ON HOLD Authors: Kuhle, B., Yang, X.L. Description: Human cytosolic Histidyl-tRNA synthetase (HisRS) with WHEP domain [[Category: Unrelease...

2019-03-13T10:18:45Z

New page: '''Unreleased structure''' The entry 6o76 is ON HOLD Authors: Kuhle, B., Yang, X.L. Description: Human cytosolic Histidyl-tRNA synthetase (HisRS) with WHEP domain [[Category: Unrelease...

New page

'''Unreleased structure'''

The entry 6o76 is ON HOLD

Authors: Kuhle, B., Yang, X.L.

Description: Human cytosolic Histidyl-tRNA synthetase (HisRS) with WHEP domain
[[Category: Unreleased Structures]]
[[Category: Yang, X.L]]
[[Category: Kuhle, B]]