5fom: Difference between revisions
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<StructureSection load='5fom' size='340' side='right'caption='[[5fom]], [[Resolution|resolution]] 2.10Å' scene=''> | <StructureSection load='5fom' size='340' side='right'caption='[[5fom]], [[Resolution|resolution]] 2.10Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[5fom]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5FOM OCA]. For a <b>guided tour on the structure components</b> use [ | <table><tr><td colspan='2'>[[5fom]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Cryptosporidium_muris_RN66 Cryptosporidium muris RN66]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5FOM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5FOM FirstGlance]. <br> | ||
</td></tr><tr id=' | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.1Å</td></tr> | ||
<tr id=' | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A2H:4-CHLORO-3-AMINOMETHYL-7-[ETHOXY]-3H-BENZO[C][1,2]OXABOROL-1-OL+MODIFIED+ADENOSINE'>A2H</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</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=5fom FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5fom OCA], [https://pdbe.org/5fom PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5fom RCSB], [https://www.ebi.ac.uk/pdbsum/5fom PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5fom ProSAT]</span></td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | |||
</table> | </table> | ||
== Function == | |||
[https://www.uniprot.org/uniprot/B6AA20_CRYMR B6AA20_CRYMR] | |||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
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__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Cryptosporidium muris RN66]] | |||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Alley MRK]] | |||
[[Category: Alley | [[Category: Bougdour A]] | ||
[[Category: Bougdour | [[Category: Cusack S]] | ||
[[Category: Cusack | [[Category: Gut J]] | ||
[[Category: Gut | [[Category: Hakimi MA]] | ||
[[Category: Hakimi | [[Category: Liu RJ]] | ||
[[Category: Liu | [[Category: Lukarska M]] | ||
[[Category: Lukarska | [[Category: Palencia A]] | ||
[[Category: Palencia | [[Category: Rosenthal PJ]] | ||
[[Category: Rosenthal | [[Category: Touquet B]] | ||
[[Category: Touquet | [[Category: Wang ED]] | ||
[[Category: Wang | |||
Latest revision as of 10:01, 19 July 2023
Crystal structure of the Cryptosporidium muris cytosolic leucyl-tRNA synthetase editing domain complex with the adduct AMP-AN6426Crystal structure of the Cryptosporidium muris cytosolic leucyl-tRNA synthetase editing domain complex with the adduct AMP-AN6426
Structural highlights
FunctionPublication Abstract from PubMedThe apicomplexan parasites Cryptosporidium and Toxoplasma are serious threats to human health. Cryptosporidiosis is a severe diarrheal disease in malnourished children and immunocompromised individuals, with the only FDA approved drug treatment currently being nitazoxanide. The existing therapies for toxoplasmosis, an important pathology in immunocompromised individuals and pregnant women, also have serious limitations. With the aim of developing alternative therapeutic options to address these health problems, we tested a number of benzoxaboroles, boron-containing compounds shown to be active against various infectious agents, for growth inhibition of Cryptosporidium parasites in mammalian cells. A 3-aminomethyl benzoxaborole, AN6426, with activity in the micromolar range and comparable to nitazoxanide, was identified and further characterised using biophysical measurements of affinity and crystal structures of complexes with the editing domain of Cryptosporidium leucyl-tRNA synthetase (LeuRS). The same compound was shown to be active against Toxoplasma parasites, with the activity being enhanced in the presence of norvaline, an amino acid that can be mischarged by LeuRS. Our observations are consistent with AN6426 inhibiting protein synthesis in both Cryptosporidium and Toxoplasma by forming a covalent adduct with tRNALeu in the LeuRS editing active site, which suggest that further exploitation of the benzoxaboroles scaffold is a valid strategy to develop novel, much needed antiparasitic agents. Cryptosporidium and Toxoplasma parasites are inhibited by a benzoxaborole targeting leucyl-tRNA synthetase.,Palencia A, Liu RJ, Lukarska M, Gut J, Bougdour A, Touquet B, Wang ED, Li X, Alley MR, Freund YR, Rosenthal PJ, Hakimi MA, Cusack S Antimicrob Agents Chemother. 2016 Jul 18. pii: AAC.00873-16. PMID:27431220[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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