View source for 3aru


==Crystal Structure Analysis of Chitinase A from Vibrio harveyi with novel inhibitors - W275G mutant complex structure with PENTOXIFYLLINE==
<StructureSection load='3aru' size='340' side='right'caption='[[3aru]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3aru]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Vibrio_harveyi Vibrio harveyi]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3ARU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3ARU 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]] 1.9&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PNX:3,7-DIMETHYL-1-(5-OXOHEXYL)-3,7-DIHYDRO-1H-PURINE-2,6-DIONE'>PNX</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=3aru FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3aru OCA], [https://pdbe.org/3aru PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3aru RCSB], [https://www.ebi.ac.uk/pdbsum/3aru PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3aru ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/Q9AMP1_VIBHA Q9AMP1_VIBHA] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Six novel inhibitors of Vibrio harveyi chitinase A (VhChiA), a family-18 chitinase homolog, were identified by in vitro screening of a library of pharmacologically active compounds. Unlike the previously identified inhibitors that mimicked the reaction intermediates, crystallographic evidence from 14 VhChiA-inhibitor complexes showed that all of the inhibitor molecules occupied the outer part of the substrate-binding cleft at two hydrophobic areas. The interactions at the aglycone location are well defined and tightly associated with Trp-397 and Trp-275, whereas the interactions at the glycone location are patchy, indicating lower affinity and a loose interaction with two consensus residues, Trp-168 and Val-205. When Trp-275 was substituted with glycine (W275G), the binding affinity toward all of the inhibitors dramatically decreased, and in most structures two inhibitor molecules were found to stack against Trp-397 at the aglycone site. Such results indicate that hydrophobic interactions are important for binding of the newly identified inhibitors by the chitinase. X-ray data and isothermal microcalorimetry showed that the inhibitors occupied the active site of VhChiA in three different binding modes, including single-site binding, independent two-site binding, and sequential two-site binding. The inhibitory effect of dequalinium in the low nanomolar range makes this compound an extremely attractive lead compound for plausible development of therapeutics against human diseases involving chitinase-mediated pathologies.

Potent family-18 chitinase inhibitors: x-ray structures, affinities, and binding mechanisms.,Pantoom S, Vetter IR, Prinz H, Suginta W J Biol Chem. 2011 Jul 8;286(27):24312-23. Epub 2011 Apr 29. PMID:21531720<ref>PMID:21531720</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 3aru" style="background-color:#fffaf0;"></div>

==See Also==
*[[Chitinase 3D structures|Chitinase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Vibrio harveyi]]
[[Category: Pantoom S]]
[[Category: Prinz H]]
[[Category: Suginta W]]
[[Category: Vetter IR]]