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'''Unreleased structure'''


The entry 5utq is ON HOLD  until Paper Publication
==Crystal structure of Burkholderia cenocepacia family 3 glycoside hydrolase (NagZ) bound to PUGNAc==
<StructureSection load='5utq' size='340' side='right' caption='[[5utq]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5utq]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5UTQ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5UTQ FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>, <scene name='pdbligand=OAN:O-(2-ACETAMIDO-2-DEOXY+D-GLUCOPYRANOSYLIDENE)+AMINO-N-PHENYLCARBAMATE'>OAN</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4mss|4mss]], [[4gnv|4gnv]], [[4g6c|4g6c]], [[5utp|5utp]]</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=5utq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5utq OCA], [http://pdbe.org/5utq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5utq RCSB], [http://www.ebi.ac.uk/pdbsum/5utq PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5utq ProSAT]</span></td></tr>
</table>
== Function ==
[[http://www.uniprot.org/uniprot/A0A125HFC0_9BURK A0A125HFC0_9BURK]] Plays a role in peptidoglycan recycling by cleaving the terminal beta-1,4-linked N-acetylglucosamine (GlcNAc) from peptide-linked peptidoglycan fragments, giving rise to free GlcNAc, anhydro-N-acetylmuramic acid and anhydro-N-acetylmuramic acid-linked peptides.[HAMAP-Rule:MF_00364][SAAS:SAAS00634279]
<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.


Authors:  
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>


Description:  
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
[[Category: Unreleased Structures]]
</div>
<div class="pdbe-citations 5utq" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Beta-N-acetylhexosaminidase]]
[[Category: Mark, B L]]
[[Category: Vadlamani, G]]
[[Category: Family 3]]
[[Category: Gh]]
[[Category: Glycoside hydrolase]]
[[Category: Hydrolase-hydrolase inhibitor complex]]
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