2xvp: Difference between revisions
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==ChiA1 from Aspergillus fumigatus, apostructure== | ==ChiA1 from Aspergillus fumigatus, apostructure== | ||
<StructureSection load='2xvp' size='340' side='right' caption='[[2xvp]], [[Resolution|resolution]] 2.00Å' scene=''> | <StructureSection load='2xvp' size='340' side='right'caption='[[2xvp]], [[Resolution|resolution]] 2.00Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[2xvp]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Aspfc Aspfc]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2XVP OCA]. For a <b>guided tour on the structure components</b> use [http:// | <table><tr><td colspan='2'>[[2xvp]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Aspfc Aspfc]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2XVP OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=2XVP FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2xtk|2xtk]], [[2xvn|2xvn]], [[2xuc|2xuc]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2xtk|2xtk]], [[2xvn|2xvn]], [[2xuc|2xuc]]</td></tr> | ||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Chitinase Chitinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.1.14 3.2.1.14] </span></td></tr> | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Chitinase Chitinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.1.14 3.2.1.14] </span></td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http:// | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=2xvp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2xvp OCA], [http://pdbe.org/2xvp PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2xvp RCSB], [http://www.ebi.ac.uk/pdbsum/2xvp PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2xvp ProSAT]</span></td></tr> | ||
</table> | </table> | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
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==See Also== | ==See Also== | ||
*[[Chitinase|Chitinase]] | *[[Chitinase 3D structures|Chitinase 3D structures]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
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[[Category: Aspfc]] | [[Category: Aspfc]] | ||
[[Category: Chitinase]] | [[Category: Chitinase]] | ||
[[Category: Large Structures]] | |||
[[Category: Aalten, D M.F van]] | [[Category: Aalten, D M.F van]] | ||
[[Category: Schuettelkopf, A W]] | [[Category: Schuettelkopf, A W]] | ||
Revision as of 15:22, 22 July 2020
ChiA1 from Aspergillus fumigatus, apostructureChiA1 from Aspergillus fumigatus, apostructure
Structural highlights
Publication Abstract from PubMedNatural products are often large, synthetically intractable molecules, yet frequently offer surprising inroads into previously unexplored chemical space for enzyme inhibitors. Argifin is a cyclic pentapeptide that was originally isolated as a fungal natural product. It competitively inhibits family 18 chitinases by mimicking the chitooligosaccharide substrate of these enzymes. Interestingly, argifin is a nanomolar inhibitor of the bacterial-type subfamily of fungal chitinases that possess an extensive chitin-binding groove, but does not inhibit the much smaller, plant-type enzymes from the same family that are involved in fungal cell division and are thought to be potential drug targets. Here we show that a small, highly efficient, argifin-derived, nine-atom fragment is a micromolar inhibitor of the plant-type chitinase ChiA1 from the opportunistic pathogen Aspergillus fumigatus. Evaluation of the binding mode with the first crystal structure of an A. fumigatus plant-type chitinase reveals that the compound binds the catalytic machinery in the same manner as observed for argifin with the bacterial-type chitinases. The structure of the complex was used to guide synthesis of derivatives to explore a pocket near the catalytic machinery. This work provides synthetically tractable plant-type family 18 chitinase inhibitors from the repurposing of a natural product. Natural product-guided discovery of a fungal chitinase inhibitor.,Rush CL, Schuttelkopf AW, Hurtado-Guerrero R, Blair DE, Ibrahim AF, Desvergnes S, Eggleston IM, van Aalten DM Chem Biol. 2010 Dec 22;17(12):1275-81. PMID:21168763[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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