3wmc: Difference between revisions
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''' | ==Crystal structure of insect beta-N-acetyl-D-hexosaminidase OfHex1 complexed with naphthalimide derivative Q2== | ||
<StructureSection load='3wmc' size='340' side='right' caption='[[3wmc]], [[Resolution|resolution]] 2.10Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[3wmc]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3WMC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3WMC FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=NF6:6-(DIMETHYLAMINO)-2-(2-{[(5-METHYL-1,3,4-THIADIAZOL-2-YL)METHYL]AMINO}ETHYL)-1H-BENZO[DE]ISOQUINOLINE-1,3(2H)-DIONE'>NF6</scene></td></tr> | |||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3nsm|3nsm]], [[3nsn|3nsn]], [[3ozo|3ozo]], [[3ozp|3ozp]], [[3s6t|3s6t]], [[3vtr|3vtr]], [[3wmb|3wmb]]</td></tr> | |||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Beta-N-acetylhexosaminidase Beta-N-acetylhexosaminidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.1.52 3.2.1.52] </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=3wmc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3wmc OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3wmc RCSB], [http://www.ebi.ac.uk/pdbsum/3wmc PDBsum]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Selective inhibition of function-specific beta-GlcNAcase has great potential in terms of drug design and biological research. The symmetrical bis-naphthalimide M-31850 was previously obtained by screening for specificity against human glycoconjugate-lytic beta-GlcNAcase. Using protein-ligand co-crystallization and molecular docking, we designed an unsymmetrical dyad of naphthalimide and thiadiazole, Q2, that changes naphthalimide specificity from against a human glycoconjugate-lytic beta-GlcNAcase to against insect and bacterial chitinolytic beta-GlcNAcases. The crystallographic and in silico studies reveal that the naphthalimide ring can be utilized to bind different parts of these enzyme homologs, providing a new starting point to design specific inhibitors. Moreover, Q2-induced closure of the substrate binding pocket is the structural basis for its 13-fold increment in inhibitory potency. Q2 is the first non-carbohydrate inhibitor against chitinolytic beta-GlcNAcases. This study provides a useful example of structure-based rationally designed inhibitors as potential pharmaceuticals or pesticides. | |||
A crystal structure-guided rational design switching non-carbohydrate inhibitors' specificity between two beta-GlcNAcase homologs.,Liu T, Guo P, Zhou Y, Wang J, Chen L, Yang H, Qian X, Yang Q Sci Rep. 2014 Aug 26;4:6188. doi: 10.1038/srep06188. PMID:25155420<ref>PMID:25155420</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Beta-N-acetylhexosaminidase]] | |||
[[Category: Chen, L.]] | |||
[[Category: Yang, Q.]] | |||
[[Category: Zhou, Y.]] | |||
[[Category: Chitinase]] | |||
[[Category: Glycosyl hydrolase]] | |||
[[Category: Hydrolase]] | |||
[[Category: Insect]] | |||
[[Category: Ostrinia furnacali]] | |||
Revision as of 08:49, 5 November 2014
Crystal structure of insect beta-N-acetyl-D-hexosaminidase OfHex1 complexed with naphthalimide derivative Q2
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