4cj1

Crystal structure of CelD in complex with affitin H3

spinqualitylabelsall models 4cj1, resolution 1.63Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4cj1 is a 2 chain structure with sequence from Acetivibrio thermocellus and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: CA, GOL, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [GUND_ACETH] This enzyme catalyzes the endohydrolysis of 1,4-beta-glucosidic linkages in cellulose, lichenin and cereal beta-D-glucans. Publication Abstract from PubMed Glycosidases are associated with various human diseases. The development of efficient and specific inhibitors may provide powerful tools to modulate their activity. However, achieving high selectivity is a major challenge given that glycosidases with different functions can have similar enzymatic mechanisms and active-site architectures. As an alternative approach to small-chemical compounds, proteinaceous inhibitors might provide a better specificity by involving a larger surface area of interaction. We report here the design and characterization of proteinaceous inhibitors that specifically target endoglycosidases representative of the two major mechanistic classes; retaining and inverting glycosidases. These inhibitors consist of artificial affinity proteins, Affitins, selected against the thermophilic CelD from Clostridium thermocellum and lysozyme from hen egg. They were obtained from libraries of Sac7d variants, which involve either the randomization of a surface or the randomization of a surface and an artificially-extended loop. Glycosidase binders exhibited affinities in the nanomolar range with no cross-recognition, with efficient inhibition of lysozyme (Ki = 45 nM) and CelD (Ki = 95 and 111 nM), high expression yields in Escherichia coli, solubility, and thermal stabilities up to 81.1 degrees C. The crystal structures of glycosidase-Affitin complexes validate our library designs. We observed that Affitins prevented substrate access by two modes of binding; covering or penetrating the catalytic site via the extended loop. In addition, Affitins formed salt-bridges with residues essential for enzymatic activity. These results lead us to propose the use of Affitins as versatile selective glycosidase inhibitors and, potentially, as enzymatic inhibitors in general. Potent and specific inhibition of glycosidases by small artificial binding proteins (affitins).,Correa A, Pacheco S, Mechaly AE, Obal G, Behar G, Mouratou B, Oppezzo P, Alzari PM, Pecorari F PLoS One. 2014 May 13;9(5):e97438. doi: 10.1371/journal.pone.0097438. eCollection, 2014. PMID:24823716 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Glucanase 3D structures

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