View source for 5utp


==Crystal structure of Burkholderia cenocepacia family 3 glycoside hydrolase (NagZ) bound to N-ethylbutyryl-PUGNAc==
<StructureSection load='5utp' size='340' side='right'caption='[[5utp]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5utp]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Burkholderia_cenocepacia Burkholderia cenocepacia]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5UTP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5UTP 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]] 2.2&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=8M7:N-[(2Z,3R,4R,5S,6R)-4,5-DIHYDROXY-6-(HYDROXYMETHYL)-2-{[(PHENYLCARBAMOYL)OXY]IMINO}TETRAHYDRO-2H-PYRAN-3-YL]-2-ETHYLBUTANAMIDE'>8M7</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=5utp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5utp OCA], [https://pdbe.org/5utp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5utp RCSB], [https://www.ebi.ac.uk/pdbsum/5utp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5utp ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/B4EA43_BURCJ B4EA43_BURCJ] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
NagZ is an N-acetyl-beta-d-glucosaminidase that participates in the peptidoglycan (PG) recycling pathway of Gram-negative bacteria by removing N-acetyl-glucosamine (GlcNAc) from PG fragments that have been excised from the cell wall during growth. The 1,6-anhydromuramoyl-peptide products generated by NagZ activate beta-lactam resistance in many Gram-negative bacteria by inducing the expression of AmpC beta-lactamase. Blocking NagZ activity can thereby suppress beta-lactam antibiotic resistance in these bacteria. The NagZ active site is dynamic and it accommodates distortion of the glycan substrate during catalysis using a mobile catalytic loop that carries a histidine residue which serves as the active site general acid/base catalyst. Here, we show that flexibility of this catalytic loop also accommodates structural differences in small molecule inhibitors of NagZ, which could be exploited to improve inhibitor specificity. X-ray structures of NagZ bound to the potent yet non-selective N-acetyl-beta-glucosaminidase inhibitor PUGNAc (O-(2-acetamido-2-deoxy-d-glucopyranosylidene) amino-N-phenylcarbamate), and two NagZ-selective inhibitors - EtBuPUG, a PUGNAc derivative bearing a 2-N-ethylbutyryl group, and MM-156, a 3-N-butyryl trihydroxyazepane, revealed that the phenylcarbamate moiety of PUGNAc and EtBuPUG completely displaces the catalytic loop from the NagZ active site to yield a catalytically incompetent form of the enzyme. In contrast, the catalytic loop was found positioned in the catalytically active conformation within the NagZ active site when bound to MM-156, which lacks the phenylcarbamate extension. Displacement of the catalytic loop by PUGNAc and its N-acyl derivative EtBuPUG alters the active site conformation of NagZ, which presents an additional strategy to improve the potency and specificity of NagZ inhibitors.

Conformational flexibility of the glycosidase NagZ allows it to bind structurally diverse inhibitors to suppress beta-lactam antibiotic resistance.,Vadlamani G, Stubbs KA, Desire J, Bleriot Y, Vocadlo DJ, Mark BL Protein Sci. 2017 Mar 28. doi: 10.1002/pro.3166. PMID:28370529<ref>PMID:28370529</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5utp" 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/>
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</StructureSection>
[[Category: Burkholderia cenocepacia]]
[[Category: Large Structures]]
[[Category: Mark BL]]
[[Category: Vadlamani G]]