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| | <StructureSection load='5t5s' size='340' side='right'caption='[[5t5s]], [[Resolution|resolution]] 2.20Å' scene=''> | | <StructureSection load='5t5s' size='340' side='right'caption='[[5t5s]], [[Resolution|resolution]] 2.20Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5t5s]] is a 1 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=5T5S OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5T5S FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5t5s]] is a 1 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=5T5S OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5T5S FirstGlance]. <br> |
| - | </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> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.202Å</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=5t5s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5t5s OCA], [https://pdbe.org/5t5s PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5t5s RCSB], [https://www.ebi.ac.uk/pdbsum/5t5s PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5t5s 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=5t5s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5t5s OCA], [http://pdbe.org/5t5s PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5t5s RCSB], [http://www.ebi.ac.uk/pdbsum/5t5s PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5t5s 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: Schimmel, P]] | + | [[Category: Schimmel P]] |
| - | [[Category: Sun, L]] | + | [[Category: Sun L]] |
| - | [[Category: Translation]]
| + | |
| - | [[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
The 20 aminoacyl tRNA synthetases (aaRSs) couple each amino acid to their cognate tRNAs. During evolution, 19 aaRSs expanded by acquiring novel noncatalytic appended domains, which are absent from bacteria and many lower eukaryotes but confer extracellular and nuclear functions in higher organisms. AlaRS is the single exception, with an appended C-terminal domain (C-Ala) that is conserved from prokaryotes to humans but with a wide sequence divergence. In human cells, C-Ala is also a splice variant of AlaRS. Crystal structures of two forms of human C-Ala, and small-angle X-ray scattering of AlaRS, showed that the large sequence divergence of human C-Ala reshaped C-Ala in a way that changed the global architecture of AlaRS. This reshaping removes the role of C-Ala in prokaryotes for docking tRNA and instead repurposes it to form a dimer interface presenting a DNA-binding groove. This groove cannot form with the bacterial ortholog. Direct DNA binding by human C-Ala, but not by bacterial C-Ala, was demonstrated. Thus, instead of acquiring a novel appended domain like other human aaRSs, which engendered novel functions, a new AlaRS architecture was created by diversifying a preexisting appended domain.
Two crystal structures reveal design for repurposing the C-Ala domain of human AlaRS.,Sun L, Song Y, Blocquel D, Yang XL, Schimmel P Proc Natl Acad Sci U S A. 2016 Dec 13;113(50):14300-14305. Epub 2016 Nov 28. PMID:27911835[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Sun L, Song Y, Blocquel D, Yang XL, Schimmel P. Two crystal structures reveal design for repurposing the C-Ala domain of human AlaRS. Proc Natl Acad Sci U S A. 2016 Dec 13;113(50):14300-14305. Epub 2016 Nov 28. PMID:27911835 doi:http://dx.doi.org/10.1073/pnas.1617316113
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