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| | ==Crystal structure of the yeast mitochondrial threonyl-tRNA synthetase (MST1) in complex with seryl sulfamoyl adenylate== | | ==Crystal structure of the yeast mitochondrial threonyl-tRNA synthetase (MST1) in complex with seryl sulfamoyl adenylate== |
| - | <StructureSection load='4eo4' size='340' side='right' caption='[[4eo4]], [[Resolution|resolution]] 2.87Å' scene=''> | + | <StructureSection load='4eo4' size='340' side='right'caption='[[4eo4]], [[Resolution|resolution]] 2.87Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4eo4]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Saccharomyces_cerevisiae_s288c Saccharomyces cerevisiae s288c]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4EO4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4EO4 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4eo4]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae_S288C Saccharomyces cerevisiae S288C]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4EO4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4EO4 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SSA:5-O-(N-(L-SERYL)-SULFAMOYL)ADENOSINE'>SSA</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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]] 2.87Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3ugq|3ugq]], [[3ugt|3ugt]], [[3uh0|3uh0]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SSA:5-O-(N-(L-SERYL)-SULFAMOYL)ADENOSINE'>SSA</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MST1, YKL194C ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=559292 Saccharomyces cerevisiae S288c])</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=4eo4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4eo4 OCA], [https://pdbe.org/4eo4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4eo4 RCSB], [https://www.ebi.ac.uk/pdbsum/4eo4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4eo4 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/Threonine--tRNA_ligase Threonine--tRNA ligase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=6.1.1.3 6.1.1.3] </span></td></tr>
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| - | <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=4eo4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4eo4 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4eo4 RCSB], [http://www.ebi.ac.uk/pdbsum/4eo4 PDBsum]</span></td></tr> | + | |
| | </table> | | </table> |
| - | <div style="background-color:#fffaf0;">
| + | == Function == |
| - | == Publication Abstract from PubMed == | + | [https://www.uniprot.org/uniprot/SYTM_YEAST SYTM_YEAST] |
| - | Accurate translation of mRNA into protein is a fundamental biological process critical for maintaining normal cellular functions. To ensure translational fidelity, aminoacyl-tRNA synthetases (aaRSs) employ pre-transfer and post-transfer editing activities to hydrolyze misactivated and mischarged amino acids, respectively. Whereas post-transfer editing, which requires either a specialized domain in aaRS or a trans-protein factor, is well described, the mechanism of pre-transfer editing is less understood. Here, we show that yeast mitochondrial threonyl-tRNA synthetase (MST1), which lacks an editing domain, utilizes pre-transfer editing to discriminate against serine. MST1 misactivates serine and edits seryl adenylate (Ser-AMP) in a tRNA-independent manner. MST1 hydrolyzes 80% of misactivated Ser-AMP at a rate 4-fold higher than that for the cognate threonyl adenylate (Thr-AMP) while releasing 20% of Ser-AMP into the solution. To understand the mechanism of pre-transfer editing, we solved the crystal structure of MST1 complexed with an analog of Ser-AMP. The binding of the Ser-AMP analog to MST1 induces conformational changes in the aminoacylation active site, and it positions a potential hydrolytic water molecule more favorably for nucleophilic attack. In addition, inhibition results reveal that the Ser-AMP analog binds the active site 100-fold less tightly than the Thr-AMP analog. In conclusion, we propose that the plasticity of the aminoacylation site in MST1 allows binding of Ser-AMP and the appropriate positioning of the hydrolytic water molecule.
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| - | The mechanism of pre-transfer editing in yeast mitochondrial threonyl-tRNA synthetase.,Ling J, Peterson KM, Simonovic I, Soll D, Simonovic M J Biol Chem. 2012 Aug 17;287(34):28518-25. doi: 10.1074/jbc.M112.372920. Epub, 2012 Jul 6. PMID:22773845<ref>PMID:22773845</ref>
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | ==See Also== |
| - | </div>
| + | *[[Aminoacyl tRNA synthetase 3D structures|Aminoacyl tRNA synthetase 3D structures]] |
| - | == References == | + | |
| - | <references/>
| + | |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Saccharomyces cerevisiae s288c]] | + | [[Category: Large Structures]] |
| - | [[Category: Threonine--tRNA ligase]] | + | [[Category: Saccharomyces cerevisiae S288C]] |
| - | [[Category: Ling, J]] | + | [[Category: Ling J]] |
| - | [[Category: Peterson, K M]] | + | [[Category: Peterson KM]] |
| - | [[Category: Simonovic, I]] | + | [[Category: Simonovic I]] |
| - | [[Category: Simonovic, M]] | + | [[Category: Simonovic M]] |
| - | [[Category: Soll, D]] | + | [[Category: Soll D]] |
| - | [[Category: Aminoacyl-trna synthetase class ii]]
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| - | [[Category: Ligase]]
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| - | [[Category: Mitochondria]]
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| - | [[Category: Threonine trna]]
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| - | [[Category: Threonyl-trna synthetase]]
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