4g85

From Proteopedia

(Difference between revisions)

Revision as of 20:29, 19 October 2022

Crystal structure of human HisRS

Structural highlights

4g85 is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

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

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).^[1] ^[2]

Publication Abstract from PubMed

Aminoacyl-tRNA synthetases (AARSs) catalyze aminoacylation of tRNAs in the cytoplasm. Surprisingly, AARSs also have critical extracellular and nuclear functions. Evolutionary pressure for new functions might be manifested by splice variants that skip only an internal catalytic domain (CD) and link noncatalytic N- and C-terminal polypeptides. Using disease-associated histidyl-tRNA synthetase (HisRS) as an example, we found an expressed 171-amino acid protein (HisRSDeltaCD) that deleted the entire CD, and joined an N-terminal WHEP to the C-terminal anticodon-binding domain (ABD). X-ray crystallography and three-dimensional NMR revealed the structures of human HisRS and HisRSDeltaCD. In contrast to homodimeric HisRS, HisRSDeltaCD is monomeric, where rupture of the ABD's packing with CD resulted in a dumbbell-like structure of flexibly linked WHEP and ABD domains. In addition, the ABD of HisRSDeltaCD presents a distinct local conformation. This natural internally deleted HisRS suggests evolutionary pressure to reshape AARS tertiary and quaternary structures for repurposing.

Internally Deleted Human tRNA Synthetase Suggests Evolutionary Pressure for Repurposing.,Xu Z, Wei Z, Zhou JJ, Ye F, Lo WS, Wang F, Lau CF, Wu J, Nangle LA, Chiang KP, Yang XL, Zhang M, Schimmel P Structure. 2012 Sep 5;20(9):1470-7. PMID:22958643^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Safka Brozkova D, Deconinck T, Griffin LB, Ferbert A, Haberlova J, Mazanec R, Lassuthova P, Roth C, Pilunthanakul T, Rautenstrauss B, Janecke AR, Zavadakova P, Chrast R, Rivolta C, Zuchner S, Antonellis A, Beg AA, De Jonghe P, Senderek J, Seeman P, Baets J. Loss of function mutations in HARS cause a spectrum of inherited peripheral neuropathies. Brain. 2015 Aug;138(Pt 8):2161-72. doi: 10.1093/brain/awv158. Epub 2015 Jun 13. PMID:26072516 doi:http://dx.doi.org/10.1093/brain/awv158
↑ Abbott JA, Meyer-Schuman R, Lupo V, Feely S, Mademan I, Oprescu SN, Griffin LB, Alberti MA, Casasnovas C, Aharoni S, Basel-Vanagaite L, Zuchner S, De Jonghe P, Baets J, Shy ME, Espinos C, Demeler B, Antonellis A, Francklyn C. Substrate interaction defects in histidyl-tRNA synthetase linked to dominant axonal peripheral neuropathy. Hum Mutat. 2018 Mar;39(3):415-432. doi: 10.1002/humu.23380. Epub 2017 Dec 26. PMID:29235198 doi:http://dx.doi.org/10.1002/humu.23380
↑ Xu Z, Wei Z, Zhou JJ, Ye F, Lo WS, Wang F, Lau CF, Wu J, Nangle LA, Chiang KP, Yang XL, Zhang M, Schimmel P. Internally Deleted Human tRNA Synthetase Suggests Evolutionary Pressure for Repurposing. Structure. 2012 Sep 5;20(9):1470-7. PMID:22958643 doi:http://dx.doi.org/10.1016/j.str.2012.08.001

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4g85"

@@ Line 1: / Line 1: @@
 ==Crystal structure of human HisRS==
-<StructureSection load='4g85' size='340' side='right' caption='[[4g85]], [[Resolution|resolution]] 3.11&Aring;' scene=''>
+<StructureSection load='4g85' size='340' side='right'caption='[[4g85]], [[Resolution|resolution]] 3.11&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4g85]] 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=4G85 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4G85 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4g85]] 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=4G85 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4G85 FirstGlance]. <br>
-</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4g84|4g84]]</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=4g85 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4g85 OCA], [https://pdbe.org/4g85 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4g85 RCSB], [https://www.ebi.ac.uk/pdbsum/4g85 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4g85 ProSAT]</span></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=4g85 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4g85 OCA], [http://pdbe.org/4g85 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4g85 RCSB], [http://www.ebi.ac.uk/pdbsum/4g85 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4g85 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).
+[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;">
 == Publication Abstract from PubMed ==
@@ Line 20: / Line 19: @@
 </div>
 <div class="pdbe-citations 4g85" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Aminoacyl tRNA synthetase 3D structures|Aminoacyl tRNA synthetase 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Histidine--tRNA ligase]]
+[[Category: Homo sapiens]]
-[[Category: Human]]
+[[Category: Large Structures]]
-[[Category: Schimmel, P]]
+[[Category: Schimmel P]]
-[[Category: Wei, Z]]
+[[Category: Wei Z]]
-[[Category: Wu, J]]
+[[Category: Wu J]]
-[[Category: Yang, X L]]
+[[Category: Yang X-L]]
-[[Category: Zhang, M]]
+[[Category: Zhang M]]
-[[Category: Zhou, J J]]
+[[Category: Zhou JJ]]
-[[Category: Ligase]]
-[[Category: Synthetase]]

4g85

From Proteopedia

Revision as of 20:29, 19 October 2022

Crystal structure of human HisRS

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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