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| | <StructureSection load='6r1m' size='340' side='right'caption='[[6r1m]], [[Resolution|resolution]] 1.50Å' scene=''> | | <StructureSection load='6r1m' size='340' side='right'caption='[[6r1m]], [[Resolution|resolution]] 1.50Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6r1m]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6R1M OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6R1M FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6r1m]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6R1M OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6R1M FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=SSA:5-O-(N-(L-SERYL)-SULFAMOYL)ADENOSINE'>SSA</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]] 1.5Å</td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Serine--tRNA_ligase Serine--tRNA ligase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=6.1.1.11 6.1.1.11] </span></td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=SSA:5-O-(N-(L-SERYL)-SULFAMOYL)ADENOSINE'>SSA</scene></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=6r1m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6r1m OCA], [http://pdbe.org/6r1m PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6r1m RCSB], [http://www.ebi.ac.uk/pdbsum/6r1m PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6r1m ProSAT]</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=6r1m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6r1m OCA], [https://pdbe.org/6r1m PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6r1m RCSB], [https://www.ebi.ac.uk/pdbsum/6r1m PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6r1m ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/A0A1X3JK72_ECOLX A0A1X3JK72_ECOLX]] Catalyzes the attachment of serine to tRNA(Ser). Is also able to aminoacylate tRNA(Sec) with serine, to form the misacylated tRNA L-seryl-tRNA(Sec), which will be further converted into selenocysteinyl-tRNA(Sec).[HAMAP-Rule:MF_00176] | + | [https://www.uniprot.org/uniprot/SYS_ECOLI SYS_ECOLI] Catalyzes the attachment of serine to tRNA(Ser) (PubMed:7537870). Is also able to aminoacylate tRNA(Sec) with serine, to form the misacylated tRNA L-seryl-tRNA(Sec), which will be further converted into selenocysteinyl-tRNA(Sec).<ref>PMID:2963963</ref> <ref>PMID:7537870</ref> <ref>PMID:8065908</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 6r1m" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 6r1m" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Aminoacyl tRNA synthetase 3D structures|Aminoacyl tRNA synthetase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| | + | [[Category: Escherichia coli]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Serine--tRNA ligase]]
| + | [[Category: Cain R]] |
| - | [[Category: Cain, R]] | + | [[Category: Roper DI]] |
| - | [[Category: Roper, D I]] | + | [[Category: Salimraj R]] |
| - | [[Category: Salimraj, R]] | + | |
| - | [[Category: Aminoacyl-trna synthetase]]
| + | |
| - | [[Category: Class ii]]
| + | |
| - | [[Category: Inhibitor]]
| + | |
| - | [[Category: Ligase]]
| + | |
| - | [[Category: Protein synthesis]]
| + | |
| Structural highlights
Function
SYS_ECOLI Catalyzes the attachment of serine to tRNA(Ser) (PubMed:7537870). Is also able to aminoacylate tRNA(Sec) with serine, to form the misacylated tRNA L-seryl-tRNA(Sec), which will be further converted into selenocysteinyl-tRNA(Sec).[1] [2] [3]
Publication Abstract from PubMed
Aminoacyl-tRNA synthetases are ubiquitous and essential enzymes for protein synthesis and also a variety of other metabolic processes, especially in bacterial species. Bacterial aminoacyl-tRNA synthetases represent attractive and validated targets for antimicrobial drug discovery if issues of prokaryotic versus eukaryotic selectivity and antibiotic resistance generation can be addressed. We have determined high-resolution X-ray crystal structures of the Escherichia coli and Staphylococcus aureus seryl-tRNA synthetases in complex with aminoacyl adenylate analogues and applied a structure-based drug discovery approach to explore and identify a series of small molecule inhibitors that selectively inhibit bacterial seryl-tRNA synthetases with greater than 2 orders of magnitude compared to their human homologue, demonstrating a route to the selective chemical inhibition of these bacterial targets.
Structure-Guided Enhancement of Selectivity of Chemical Probe Inhibitors Targeting Bacterial Seryl-tRNA Synthetase.,Cain R, Salimraj R, Punekar AS, Bellini D, Fishwick CWG, Czaplewski L, Scott DJ, Harris G, Dowson CG, Lloyd AJ, Roper DI J Med Chem. 2019 Nov 14;62(21):9703-9717. doi: 10.1021/acs.jmedchem.9b01131. Epub, 2019 Nov 5. PMID:31626547[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Leinfelder W, Zehelein E, Mandrand-Berthelot MA, Böck A. Gene for a novel tRNA species that accepts L-serine and cotranslationally inserts selenocysteine. Nature. 1988 Feb 25;331(6158):723-5. PMID:2963963 doi:10.1038/331723a0
- ↑ Vincent C, Borel F, Willison JC, Leberman R, Härtlein M. Seryl-tRNA synthetase from Escherichia coli: functional evidence for cross-dimer tRNA binding during aminoacylation. Nucleic Acids Res. 1995 Apr 11;23(7):1113-8. PMID:7537870 doi:10.1093/nar/23.7.1113
- ↑ Borel F, Vincent C, Leberman R, Härtlein M. Seryl-tRNA synthetase from Escherichia coli: implication of its N-terminal domain in aminoacylation activity and specificity. Nucleic Acids Res. 1994 Aug 11;22(15):2963-9. PMID:8065908 doi:10.1093/nar/22.15.2963
- ↑ Cain R, Salimraj R, Punekar AS, Bellini D, Fishwick CWG, Czaplewski L, Scott DJ, Harris G, Dowson CG, Lloyd AJ, Roper DI. Structure-Guided Enhancement of Selectivity of Chemical Probe Inhibitors Targeting Bacterial Seryl-tRNA Synthetase. J Med Chem. 2019 Nov 14;62(21):9703-9717. doi: 10.1021/acs.jmedchem.9b01131. Epub, 2019 Nov 5. PMID:31626547 doi:http://dx.doi.org/10.1021/acs.jmedchem.9b01131
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