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==Crystal Structure Analysis of Chitinase A from Vibrio harveyi with novel inhibitors - complex structure with Propentofylline== | ==Crystal Structure Analysis of Chitinase A from Vibrio harveyi with novel inhibitors - complex structure with Propentofylline== | ||
<StructureSection load='3arx' size='340' side='right' caption='[[3arx]], [[Resolution|resolution]] 1.16Å' scene=''> | <StructureSection load='3arx' size='340' side='right' caption='[[3arx]], [[Resolution|resolution]] 1.16Å' scene=''> | ||
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CHIA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=669 "Achromobacter harveyi" Johnson and Shunk 1936])</td></tr> | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CHIA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=669 "Achromobacter harveyi" Johnson and Shunk 1936])</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://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3arx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3arx OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3arx RCSB], [http://www.ebi.ac.uk/pdbsum/3arx PDBsum]</span></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=3arx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3arx OCA], [http://pdbe.org/3arx PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3arx RCSB], [http://www.ebi.ac.uk/pdbsum/3arx PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3arx ProSAT]</span></td></tr> | ||
</table> | </table> | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | </div> | ||
<div class="pdbe-citations 3arx" style="background-color:#fffaf0;"></div> | |||
==See Also== | ==See Also== | ||
Revision as of 21:22, 5 August 2016
Crystal Structure Analysis of Chitinase A from Vibrio harveyi with novel inhibitors - complex structure with PropentofyllineCrystal Structure Analysis of Chitinase A from Vibrio harveyi with novel inhibitors - complex structure with Propentofylline
Structural highlights
Publication Abstract from PubMedSix 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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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