3wmc

From Proteopedia

(Difference between revisions)

Current revision

Crystal structure of insect beta-N-acetyl-D-hexosaminidase OfHex1 complexed with naphthalimide derivative Q2

Structural highlights

3wmc is a 1 chain structure with sequence from Ostrinia furnacalis. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.095Å
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

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).^[1] ^[2]

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^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Yang Q, Liu T, Liu F, Qu M, Qian X. A novel beta-N-acetyl-D-hexosaminidase from the insect Ostrinia furnacalis (Guenée). FEBS J. 2008 Nov;275(22):5690-702. PMID:18959754 doi:10.1111/j.1742-4658.2008.06695.x
↑ Liu T, Zhang H, Liu F, Wu Q, Shen X, Yang Q. Structural Determinants of an Insect {beta}-N-Acetyl-D-hexosaminidase Specialized as a Chitinolytic Enzyme. J Biol Chem. 2011 Feb 11;286(6):4049-58. Epub 2010 Nov 24. PMID:21106526 doi:10.1074/jbc.M110.184796
↑ Liu T, Guo P, Zhou Y, Wang J, Chen L, Yang H, Qian X, Yang Q. A crystal structure-guided rational design switching non-carbohydrate inhibitors' specificity between two beta-GlcNAcase homologs. Sci Rep. 2014 Aug 26;4:6188. doi: 10.1038/srep06188. PMID:25155420 doi:http://dx.doi.org/10.1038/srep06188

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3wmc"

Categories: Large Structures | Ostrinia furnacalis | Chen L | Yang Q | Zhou Y

@@ Line 3: / Line 3: @@
 <StructureSection load='3wmc' size='340' side='right'caption='[[3wmc]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3wmc]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Asian_corn_borer Asian corn borer]. 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>
+<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='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>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.095&#8491;</td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3nsm|3nsm]], [[3nsn|3nsn]], [[3ozo|3ozo]], [[3ozp|3ozp]], [[3s6t|3s6t]], [[3vtr|3vtr]], [[3wmb|3wmb]]</div></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='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">OfHex1 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=93504 Asian corn borer])</td></tr>
-<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Beta-N-acetylhexosaminidase Beta-N-acetylhexosaminidase], with EC number [https://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'>[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 ==
@@ Line 28: / Line 28: @@
 __TOC__
 </StructureSection>
-[[Category: Asian corn borer]]
-[[Category: Beta-N-acetylhexosaminidase]]
 [[Category: Large Structures]]
-[[Category: Chen, L]]
+[[Category: Ostrinia furnacalis]]
-[[Category: Yang, Q]]
+[[Category: Chen L]]
-[[Category: Zhou, Y]]
+[[Category: Yang Q]]
-[[Category: Chitinase]]
+[[Category: Zhou Y]]
-[[Category: Glycosyl hydrolase]]
-[[Category: Hydrolase]]
-[[Category: Insect]]
-[[Category: Ostrinia furnacali]]

3wmc

From Proteopedia

Current revision

Crystal structure of insect beta-N-acetyl-D-hexosaminidase OfHex1 complexed with naphthalimide derivative Q2

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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