6r1o: Difference between revisions

Latest revision as of 12:13, 24 January 2024

Crystal structure of E. coli seryl-tRNA synthetase complexed to a seryl sulfamoyl adenosine derivative

Structural highlights

6r1o is a 1 chain structure with sequence from Escherichia coli. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.6Å
Ligands:	CL, DMS, EDO, JPE, SO4, TRS
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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.

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:https://dx.doi.org/10.1021/acs.jmedchem.9b01131

Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] 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

[2] 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

[3] 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

[4] 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:https://dx.doi.org/10.1021/acs.jmedchem.9b01131

[1]

[2]

[3]

[4]

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 6r1o is ON HOLD
+==Crystal structure of E. coli seryl-tRNA synthetase complexed to a seryl sulfamoyl adenosine derivative==
+<StructureSection load='6r1o' size='340' side='right'caption='[[6r1o]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[6r1o]] is a 1 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=6R1O OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6R1O FirstGlance]. <br>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.6&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=JPE:[(2~{R},3~{S},4~{R},5~{R})-5-(6-azanyl-2-pyridin-3-yl-purin-9-yl)-3,4-bis(oxidanyl)oxolan-2-yl]methyl+~{N}-[(2~{S})-2-azanyl-3-oxidanyl-propanoyl]sulfamate'>JPE</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=TRS:2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>TRS</scene></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=6r1o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6r1o OCA], [https://pdbe.org/6r1o PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6r1o RCSB], [https://www.ebi.ac.uk/pdbsum/6r1o PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6r1o ProSAT]</span></td></tr>
+</table>
+== Function ==
+[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;">
+== 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.
-Authors: Salimraj, R., Cain, R., Roper, D.I.
+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<ref>PMID:31626547</ref>
-Description: Crystal structure of E. coli seryl-tRNA synthetase complexed to a seryl sulfamoyl adenosine derivative
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
-[[Category: Salimraj, R]]
+<div class="pdbe-citations 6r1o" style="background-color:#fffaf0;"></div>
-[[Category: Roper, D.I]]
-[[Category: Cain, R]]
+==See Also==
+*[[Aminoacyl tRNA synthetase 3D structures|Aminoacyl tRNA synthetase 3D structures]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Escherichia coli]]
+[[Category: Large Structures]]
+[[Category: Cain R]]
+[[Category: Roper DI]]
+[[Category: Salimraj R]]

6r1o: Difference between revisions

Latest revision as of 12:13, 24 January 2024

Crystal structure of E. coli seryl-tRNA synthetase complexed to a seryl sulfamoyl adenosine derivative

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

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