View source for 4ycv


==Crystal structure of cladosporin in complex with plasmodium lysyl-tRNA synthetase==
<StructureSection load='4ycv' size='340' side='right'caption='[[4ycv]], [[Resolution|resolution]] 3.41&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4ycv]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Plasmodium_falciparum_NF54 Plasmodium falciparum NF54]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4YCV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4YCV 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]] 3.406&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=KRS:CLADOSPORIN'>KRS</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=4ycv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ycv OCA], [https://pdbe.org/4ycv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ycv RCSB], [https://www.ebi.ac.uk/pdbsum/4ycv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ycv ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/W7JP72_PLAFO W7JP72_PLAFO] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Pharmaceutical inhibitors of aminoacyl-tRNA synthetases demand high species and family specificity. The antimalarial ATP-mimetic cladosporin selectively inhibits Plasmodium falciparum LysRS (PfLysRS). How the binding to a universal ATP site achieves the specificity is unknown. Here we report three crystal structures of cladosporin with human LysRS, PfLysRS, and a Pf-like human LysRS mutant. In all three structures, cladosporin occupies the class defining ATP-binding pocket, replacing the adenosine portion of ATP. Three residues holding the methyltetrahydropyran moiety of cladosporin are critical for the specificity of cladosporin against LysRS over other class II tRNA synthetase families. The species-exclusive inhibition of PfLysRS is linked to a structural divergence beyond the active site that mounts a lysine-specific stabilizing response to binding cladosporin. These analyses reveal that inherent divergence of tRNA synthetase structural assembly may allow for highly specific inhibition even through the otherwise universal substrate binding pocket and highlight the potential for structure-driven drug development.

Structural Basis for Specific Inhibition of tRNA Synthetase by an ATP Competitive Inhibitor.,Fang P, Han H, Wang J, Chen K, Chen X, Guo M Chem Biol. 2015 Jun 18;22(6):734-44. doi: 10.1016/j.chembiol.2015.05.007. Epub, 2015 Jun 11. PMID:26074468<ref>PMID:26074468</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4ycv" style="background-color:#fffaf0;"></div>

==See Also==
*[[Aminoacyl tRNA synthetase 3D structures|Aminoacyl tRNA synthetase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Plasmodium falciparum NF54]]
[[Category: Fang P]]
[[Category: Guo M]]
[[Category: Wang J]]