3wmc: Difference between revisions
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New page: '''Unreleased structure''' The entry 3wmc is ON HOLD Authors: Chen,L, Zhou.Y, Chen.L, Yang.Q Description: Crystal structure of insect beta-N-acetyl-D-hexosaminidase OfHex1 complexed wi... |
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The | ==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 with sequence from [https://en.wikipedia.org/wiki/Ostrinia_furnacalis Ostrinia furnacalis]. 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 [https://proteopedia.org/fgij/fg.htm?mol=3WMC 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]] 2.095Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3wmc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3wmc OCA], [https://pdbe.org/3wmc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3wmc RCSB], [https://www.ebi.ac.uk/pdbsum/3wmc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3wmc ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/HEXC_OSTFU HEXC_OSTFU] Hydrolyzes one beta-GlcNAc unit at a time from the non-reducing ends of substrates, with a preference for shorter substrates. The 2-acetamido group and the beta-glycoside bond linkage in the substrate are required for its activity. Active with p-nitrophenyl (pNP)-beta-GlcNAc, pNP-beta-GalNAc and chitooligosaccharides (degree of polymerization from 2 to 6), but not with the complex N-glycan substrate (GlcNAcbeta-1,2Manalpha-1,6)(GlcNAcbeta-1,2Manalpha-1,3)Manbeta-1,4GlcNAcbeta-1,4GlcNAc-PA (GnGn-PA), pNP-alpha-GlcNAc or with the long polymer colloidal chitin. Involved in chitin catabolism (PubMed:18959754). Involved in the degradation of old cuticle during the pupation stage (PubMed:21106526).<ref>PMID:18959754</ref> <ref>PMID:21106526</ref> | |||
<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> | |||
<div class="pdbe-citations 3wmc" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Beta-Hexosaminidase|Beta-Hexosaminidase]] | |||
*[[Beta-Hexosaminidase 3D structures|Beta-Hexosaminidase 3D structures]] | |||
*[[Beta-N-acetylhexosaminidase 3D structures|Beta-N-acetylhexosaminidase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Ostrinia furnacalis]] | |||
[[Category: Chen L]] | |||
[[Category: Yang Q]] | |||
[[Category: Zhou Y]] | |||
