View source for 6s30


==Crystal Structure of Seryl-tRNA Synthetase from Klebsiella pneumoniae==
<StructureSection load='6s30' size='340' side='right'caption='[[6s30]], [[Resolution|resolution]] 2.41&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6s30]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Klebsiella_pneumoniae Klebsiella pneumoniae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6S30 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6S30 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]] 2.41&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</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=6s30 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6s30 OCA], [https://pdbe.org/6s30 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6s30 RCSB], [https://www.ebi.ac.uk/pdbsum/6s30 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6s30 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/SYS_KLEP7 SYS_KLEP7] 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).
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The pyrimidine-containing Trojan horse antibiotics albomycin and a recently discovered cytidine-containing microcin C analog target the class II seryl- and aspartyl-tRNA synthetases (serRS and aspRS), respectively. The active component of these compounds are competitive inhibitors that mimic the aminoacyl-adenylate intermediate. How they effectively substitute for the interactions mediated by the canonical purine group is unknown. Employing non-hydrolysable aminoacyl-sulfamoyl nucleosides substituting the base with cytosine, uracil and N3-methyluracil the structure-activity relationship of the natural compounds was evaluated. In vitro using E. coli serRS and aspRS, the best compounds demonstrated IC50 values in the low nanomolar range, with a clear preference for cytosine or N3-methyluracil over uracil. X-ray crystallographic structures of K. pneumoniae serRS and T. thermophilus aspRS in complex with the compounds showed the contribution of structured waters and residues in the conserved motif-2 loop in defining base preference. Utilizing the N3-methyluracil bound serRS structure, MD simulations of the fully modified albomycin base were performed to identify the interacting network that drives stable association. This analysis pointed to key interactions with a methionine in the motif-2 loop. Interestingly, this residue is mutated to a glycine in a second serRS (serRS2) found in albomycin-producing actinobacteria possessing self-immunity to this antibiotic. A comparative study demonstrated that serRS2 is poorly inhibited by the pyrimidine-containing intermediate analogs, and an equivalent mutation in E. coli serRS significantly decreased the affinity of the cytosine congener. These findings highlight the crucial role of dynamics and solvation of the motif-2 loop in modulating the binding of the natural antibiotics.

Structural insights into the binding of natural pyrimidine-based inhibitors of class II aminoacyl-tRNA synthetases.,Pang L, Nautiyal M, De Graef S, Gadakh B, Zorzini V, Economou A, Strelkov SV, Van Aerschot A, Weeks SD ACS Chem Biol. 2019 Dec 23. doi: 10.1021/acschembio.9b00887. PMID:31869198<ref>PMID:31869198</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6s30" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Klebsiella pneumoniae]]
[[Category: Large Structures]]
[[Category: De Graef S]]
[[Category: Pang L]]
[[Category: Strelkov SV]]
[[Category: Weeks SD]]