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4phc

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Revision as of 08:40, 22 November 2017

Crystal Structure of a human cytosolic histidyl-tRNA synthetase, histidine-bound

Structural highlights

4phc is a 4 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Gene:	HARS, HRS (HUMAN)
Activity:	Histidine--tRNA ligase, with EC number 6.1.1.21
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[SYHC_HUMAN] Defects in HARS are a cause of Usher syndrome type 3B (USH3B) [MIM: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.^[1] 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).

Publication Abstract from PubMed

As part of a project aimed at obtaining selective inhibitors and drug-like compounds targeting tRNA synthetases from trypanosomatids, we have elucidated the crystal structure of human cytosolic histidyl-tRNA synthetase (Hs-cHisRS) in complex with histidine in order to be able to compare human and parasite enzymes. The resultant structure of Hs-cHisRS*His represents the substrate-bound state (H-state) of the enzyme. It provides an interesting opportunity to compare with ligand-free and imidazole-bound structures Hs-cHisRS published recently, both of which represent the ligand-free state (F-state) of the enzyme. The H-state Hs-cHisRS undergoes conformational changes in active site residues and several conserved motif of HisRS, compared to F-state structures. The histidine forms eight hydrogen bonds with HisRS of which six engage the amino and carboxylate groups of this amino acid. The availability of published imidazole-bound structure provides a unique opportunity to dissect the structural roles of individual chemical groups of histidine. The analysis revealed the importance of the amino and carboxylate groups, of the histidine in leading to these dramatic conformational changes of the H-state. Further, comparison with previously published trypanosomatid HisRS structures reveals a pocket in the F-state of the parasite enzyme that may provide opportunities for developing specific inhibitors of Trypanosoma brucei HisRS.

Comparison of histidine recognition in human and trypanosomatid histidyl-tRNA synthetases.,Koh CY, Wetzel AB, de van der Schueren WJ, Hol WG Biochimie. 2014 Nov;106:111-20. doi: 10.1016/j.biochi.2014.08.005. Epub 2014 Aug , 20. PMID:25151410^[2]

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

References

↑ Puffenberger EG, Jinks RN, Sougnez C, Cibulskis K, Willert RA, Achilly NP, Cassidy RP, Fiorentini CJ, Heiken KF, Lawrence JJ, Mahoney MH, Miller CJ, Nair DT, Politi KA, Worcester KN, Setton RA, Dipiazza R, Sherman EA, Eastman JT, Francklyn C, Robey-Bond S, Rider NL, Gabriel S, Morton DH, Strauss KA. Genetic mapping and exome sequencing identify variants associated with five novel diseases. PLoS One. 2012;7(1):e28936. doi: 10.1371/journal.pone.0028936. Epub 2012 Jan 17. PMID:22279524 doi:10.1371/journal.pone.0028936
↑ Koh CY, Wetzel AB, de van der Schueren WJ, Hol WG. Comparison of histidine recognition in human and trypanosomatid histidyl-tRNA synthetases. Biochimie. 2014 Nov;106:111-20. doi: 10.1016/j.biochi.2014.08.005. Epub 2014 Aug , 20. PMID:25151410 doi:http://dx.doi.org/10.1016/j.biochi.2014.08.005

1 Structural highlights
2 Disease
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

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

@@ Line 3: / Line 3: @@
 <StructureSection load='4phc' size='340' side='right' caption='[[4phc]], [[Resolution|resolution]] 2.84&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4phc]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4PHC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4PHC FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4phc]] is a 4 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=4PHC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4PHC FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=HIS:HISTIDINE'>HIS</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='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=4phc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4phc OCA], [http://pdbe.org/4phc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4phc RCSB], [http://www.ebi.ac.uk/pdbsum/4phc PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4phc ProSAT]</span></td></tr>
@@ Line 24: / Line 25: @@
 </StructureSection>
 [[Category: Histidine--tRNA ligase]]
+[[Category: Human]]
 [[Category: Hol, W G.J]]
 [[Category: Koh, C Y]]
@@ Line 32: / Line 34: @@
 [[Category: Cytoplasmic]]
 [[Category: Hisr]]
-[[Category: Human]]
 [[Category: Ligase]]
 [[Category: Nucleotide binding]]

4phc

From Proteopedia

Revision as of 08:40, 22 November 2017

Crystal Structure of a human cytosolic histidyl-tRNA synthetase, histidine-bound

Structural highlights

Disease

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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