4az5

Differential inhibition of the tandem GH20 catalytic modules in the pneumococcal exo-beta-D-N-acetylglucosaminidase, StrH

spinqualitylabelsall models 4az5, resolution 1.73Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4az5 is a 1 chain structure with sequence from Streptococcus pneumoniae TIGR4. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.73Å Ligands: EDO, MG, NGW, PE4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function STRH_STRPN Publication Abstract from PubMed Streptococcus pneumoniae produces a cell-surface attached beta-N-acetylglucosaminidase called StrH that is used by this pathogen to process the termini of host complex N-linked glycans. N-Acetyl-d-glucosamine-thiazoline (NAG-Thiazoline, NGT) and O-(2-acetamido-2-deoxy-d-glucopyranosylidene)amino N-phenyl carbamate (PUGNAc) are inhibitors of the two family 20 glycoside hydrolase catalytic modules within StrH and these inhibitors have proven useful in modulating the activity of StrH in assays that model aspects of the host-bacterium interaction. Here we explore the molecular basis of StrH inhibition through structural, kinetic, thermodynamic and site-directed mutagenic analyses using the recombinantly produced independent catalytic modules of StrH (GH20A and GH20B) and the inhibitors NGT and PUGNAc. The results reveal a similar binding mode of the sugar moiety of these inhibitors at the -1 subsite in the active sites of GH20A and GH20B. The lower affinity of NGT as compared to PUGNAc for these catalytic modules can be attributed to the hydrophobic phenylcarbamate moiety of PUGNAc that is absent in NGT. This moiety also displayed variations in its interactions with the active sites of GH20A and GH20B that provide a rationale for the 400-fold difference observed in the Ki values of this compound for these two beta-N-acetylglucosaminidase catalytic modules. Inhibition of the family 20 glycoside hydrolase catalytic modules in the Streptococcus pneumoniae exo-beta-d-N-acetylglucosaminidase, StrH.,Pluvinage B, Stubbs KA, Hattie M, Vocadlo DJ, Boraston AB Org Biomol Chem. 2013 Oct 16. PMID:24132305 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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