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| | <StructureSection load='5knn' size='340' side='right'caption='[[5knn]], [[Resolution|resolution]] 2.68Å' scene=''> | | <StructureSection load='5knn' size='340' side='right'caption='[[5knn]], [[Resolution|resolution]] 2.68Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5knn]] is a 8 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=5KNN OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5KNN FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5knn]] is a 8 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=5KNN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5KNN FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A5A:5-O-(N-(L-ALANYL)-SULFAMOYL)ADENOSINE'>A5A</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]] 2.68Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">AARS ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A5A:5-O-(N-(L-ALANYL)-SULFAMOYL)ADENOSINE'>A5A</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Alanine--tRNA_ligase Alanine--tRNA ligase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=6.1.1.7 6.1.1.7] </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=5knn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5knn OCA], [https://pdbe.org/5knn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5knn RCSB], [https://www.ebi.ac.uk/pdbsum/5knn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5knn ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5knn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5knn OCA], [http://pdbe.org/5knn PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5knn RCSB], [http://www.ebi.ac.uk/pdbsum/5knn PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5knn ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/SYAC_HUMAN SYAC_HUMAN]] Autosomal dominant Charcot-Marie-Tooth disease type 2N. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. | + | [https://www.uniprot.org/uniprot/SYAC_HUMAN SYAC_HUMAN] Autosomal dominant Charcot-Marie-Tooth disease type 2N. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/SYAC_HUMAN SYAC_HUMAN]] Catalyzes the attachment of alanine to tRNA(Ala) in a two-step reaction: alanine is first activated by ATP to form Ala-AMP and then transferred to the acceptor end of tRNA(Ala). Also edits incorrectly charged tRNA(Ala) via its editing domain.[HAMAP-Rule:MF_03133] | + | [https://www.uniprot.org/uniprot/SYAC_HUMAN SYAC_HUMAN] Catalyzes the attachment of alanine to tRNA(Ala) in a two-step reaction: alanine is first activated by ATP to form Ala-AMP and then transferred to the acceptor end of tRNA(Ala). Also edits incorrectly charged tRNA(Ala) via its editing domain.[HAMAP-Rule:MF_03133] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Alanine--tRNA ligase]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Human]]
| + | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: He, W]] | + | [[Category: He W]] |
| - | [[Category: Sun, L]] | + | [[Category: Sun L]] |
| - | [[Category: Yang, X L]] | + | [[Category: Yang X-L]] |
| - | [[Category: Ligase]]
| + | |
| - | [[Category: Trna synthetase]]
| + | |
| Structural highlights
Disease
SYAC_HUMAN Autosomal dominant Charcot-Marie-Tooth disease type 2N. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry.
Function
SYAC_HUMAN Catalyzes the attachment of alanine to tRNA(Ala) in a two-step reaction: alanine is first activated by ATP to form Ala-AMP and then transferred to the acceptor end of tRNA(Ala). Also edits incorrectly charged tRNA(Ala) via its editing domain.[HAMAP-Rule:MF_03133]
Publication Abstract from PubMed
Fidelity of translation, which is predominately dictated by the accuracy of aminoacyl-tRNA synthetases in pairing amino acids with correct tRNAs, is of central importance in biology. Yet, deliberate modifications of translational fidelity can be beneficial. Here we found human and not E. coli AlaRS has an intrinsic capacity for mis-pairing alanine onto non-alanyl-tRNAs including tRNACys. Consistently, a cysteine-to-alanine substitution was found in a reporter protein expressed in human cells. All human AlaRS-mischarged tRNAs have a G4:U69 base pair in the acceptor stem. The base pair is required for the mischarging. By solving the crystal structure of human AlaRS and comparing it to that of E. coli AlaRS, we identified a key sequence divergence between eukaryotes and bacteria that influences mischarging. Thus, the expanded tRNA specificity of AlaRS appears to be an evolutionary gain-of-function to provide posttranscriptional alanine substitutions in eukaryotic proteins for potential regulations.
Evolutionary gain of alanine mischarging to non-cognate tRNAs with a G4:U69 base pair.,Sun L, Gomes AC, He W, Zhou H, Wang X, Pan DW, Schimmel P, Pan T, Yang XL J Am Chem Soc. 2016 Sep 13. PMID:27622773[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Sun L, Gomes AC, He W, Zhou H, Wang X, Pan DW, Schimmel P, Pan T, Yang XL. Evolutionary gain of alanine mischarging to non-cognate tRNAs with a G4:U69 base pair. J Am Chem Soc. 2016 Sep 13. PMID:27622773 doi:http://dx.doi.org/10.1021/jacs.6b07121
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