2xvn: Difference between revisions
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[[ | ==A. FUMIGATUS CHITINASE A1 PHENYL-METHYLGUANYLUREA COMPLEX== | ||
<StructureSection load='2xvn' size='340' side='right' caption='[[2xvn]], [[Resolution|resolution]] 2.35Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[2xvn]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Aspergillus_fumigatus Aspergillus fumigatus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2XVN OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2XVN FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=KLS:1-METHYL-3-(N-PHENYLCARBAMIMIDOYL)UREA'>KLS</scene></td></tr> | |||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2xuc|2xuc]], [[2xvp|2xvp]]</td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2xvn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2xvn OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2xvn RCSB], [http://www.ebi.ac.uk/pdbsum/2xvn PDBsum]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Natural 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<ref>PMID:21168763</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
==See Also== | ==See Also== | ||
*[[Chitinase|Chitinase]] | *[[Chitinase|Chitinase]] | ||
== References == | |||
== | <references/> | ||
< | __TOC__ | ||
</StructureSection> | |||
[[Category: Aspergillus fumigatus]] | [[Category: Aspergillus fumigatus]] | ||
[[Category: Aalten, D M.F Van.]] | [[Category: Aalten, D M.F Van.]] | ||
