1jak

Streptomyces plicatus beta-N-acetylhexosaminidase in Complex with (2R,3R,4S,5R)-2-acetamido-3,4-dihydroxy-5-hydroxymethyl-piperidinium chloride (IFG)Streptomyces plicatus beta-N-acetylhexosaminidase in Complex with (2R,3R,4S,5R)-2-acetamido-3,4-dihydroxy-5-hydroxymethyl-piperidinium chloride (IFG)

Structural highlights 1jak is a 1 chain structure with sequence from Streptomyces plicatus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.75Å Ligands: , , , Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function O85361_STRPL Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed Azasugar inhibitors of the isofagomine class are potent competitive inhibitors of configuration-retaining beta-glycosidases. This potency results from the formation of a strong electrostatic interaction between a protonated endocyclic nitrogen at the "anomeric" center of the inhibitor and the catalytic nucleophile of the enzyme. Although the majority of retaining beta-glycosidases use a mechanism involving a carboxylate residue as a nucleophile, Streptomyces plicatus beta-N-acetylhexos-aminidase (SpHEX) and related family 20 glycosidases lack such a catalytic residue and use instead the carbonyl oxygen of the 2-acetamido group of the substrate as a nucleophile to "attack" the anomeric center. Thus, a strong electrostatic interaction between the inhibitor and enzyme is not expected to occur; nonetheless, the 1-N-azasugar (2R,3R,4S,5R)-2-acetamido-3,4-dihydroxy-5-hydroxymethyl-piperidinium hydrochloride (GalNAc-isofagomine.HCl), which was synthesized and assayed for its ability to inhibit SpHEX, was found to be a potent competitive inhibitor of the enzyme (K(i) = 2.7 microm). A crystallographic complex of GalNAc-isofagomine bound to SpHEX was solved and refined to 1.75 A and revealed that the lack of a strong electrostatic interaction between the "anomeric" center of GalNAc-isofagomine and SpHEX is compensated for by a novel 2.8-A hydrogen bond formed between the equatorial proton of the endocyclic nitrogen of the azasugar ring and the carboxylate of the general acid-base residue Glu-314 of SpHEX. This interaction appears to contribute to the unexpected potency of GalNAc-isofagomine toward SpHEX. Biochemical and structural assessment of the 1-N-azasugar GalNAc-isofagomine as a potent family 20 beta-N-acetylhexosaminidase inhibitor.,Mark BL, Vocadlo DJ, Zhao D, Knapp S, Withers SG, James MN J Biol Chem. 2001 Nov 9;276(45):42131-7. Epub 2001 Aug 24. PMID:11522797 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

spinqualitylabelsall models 1jak, resolution 1.75Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image