5utr | pdb_00005utr

Crystal structure of Burkholderia cenocepacia family 3 glycoside hydrolase (NagZ) bound to (3S,4R,5R,6S)-3-butyryl-4,5,6-trihydroxyazepane

spinqualitylabelsall models 5utr, resolution 2.15Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5utr is a 2 chain structure with sequence from Burkholderia cenocepacia. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.15Å Ligands: 8MP Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function B4EA43_BURCJ 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Beta-Hexosaminidase Beta-Hexosaminidase 3D structures Beta-N-acetylhexosaminidase 3D structures

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