1w3l

ENDOGLUCANASE CEL5A FROM BACILLUS AGARADHAERENS IN COMPLEX WITH CELLOTRI DERIVED-TETRAHYDROOXAZINE

spinqualitylabelsall models 1w3l, resolution 1.04Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 1w3l is a 1 chain structure with sequence from Salipaludibacillus agaradhaerens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.04Å Ligands: BGC, GOL, OXZ, PRD_900005, SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function GUN5_SALAG 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 The understanding of transition state mimicry in glycoside hydrolysis is increasingly important both in the quest for novel specific therapeutic agents and for the deduction of enzyme function and mechanism. To aid comprehension, inhibitors can be characterized through kinetic, thermodynamic, and structural dissection to build an "inhibition profile." Here we dissect the binding of a tetrahydrooxazine inhibitor and its derivatives, which display Ki values around 500 nm. X-ray structures with both a beta-glucosidase, at 2 A resolution, and an endoglucanase at atomic (approximately 1 A) resolution reveal similar interactions between the tetrahydrooxazine inhibitor and both enzymes. Kinetic analyses reveal the pH dependence of kcat/Km and 1/Ki with both enzyme systems, and isothermal titration calorimetry unveils the enthalpic and entropic contributions to beta-glucosidase inhibition. The pH dependence of enzyme activity mirrored that of 1/Ki in both enzymes, unlike the cases of isofagomine and 1-deoxynojirimycin that have been characterized previously. Calorimetric dissection reveals a large favorable enthalpy that is partially offset by an unfavorable entropy upon binding. In terms of the similar profile for the pH dependence of 1/Ki and the pH dependence of kcat/Km, the significant enthalpy of binding when compared with other glycosidase inhibitors, and the tight binding at the optimal pH of the enzymes tested, tetrahydrooxazine and its derivatives are a significantly better class of glycosidase inhibitor than previously assumed. Structural, thermodynamic, and kinetic analyses of tetrahydrooxazine-derived inhibitors bound to beta-glucosidases.,Gloster TM, Macdonald JM, Tarling CA, Stick RV, Withers SG, Davies GJ J Biol Chem. 2004 Nov 19;279(47):49236-42. Epub 2004 Sep 8. PMID:15356002 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Glucanase 3D structures

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