title: The studies on substrate, product and inhibitor binding to a wild-type and neuronopathic form of human acid-beta-glucosidase.
abstract: Gaucher disease is a lysosomal storage disorder caused by deficiency of human acid beta-glucosidase. Recent x-ray structural elucidation of the enzyme alone and in the presence of its inhibitor was done, which provided an excellent template for further studies on the binding of substrate, product and inhibitor. To draw correlations between the clinical manifestation of the disease driven by point mutations, L444P and L444R, and the placement and function of putative S-binding sites, the presented theoretical studies were undertaken, which comprised of molecular dynamics and molecular docking methods. The obtained results indicate the D443 and D445 residues as extremely important for physiological functionality of an enzyme. They also show, although indirectly, that binding of the substrate is influenced by an interplay of E235 and E334 residues, constituting putative substrate binding site, and the region flanked by D435 and D445 residues.
authors: Department of Biotechnology, University of Rzeszow, ul Sokolowska 26, 36-100, Kolbuszowa, Poland. izubrzyc@univ.rzeszow.pl
authors: Igor Z
authors: IZ
authors: Zubrzycki
authors: Agnieszka
authors: A
authors: Borcz
authors: Magdalena
authors: M
authors: Wiacek
authors: Wojciech
authors: W
authors: Hagner
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D001665:Binding Sites; D005776:Gaucher Disease / Q000201:enzymology*; D005962:Glucosylceramidase / Q000737:chemistry*; D006801:Humans; D017354:Point Mutation; D011994:Recombinant Proteins / Q000737:chemistry; D014961:X-Ray Diffraction
chemical_list: D011994:Recombinant Proteins; D005962:Glucosylceramidase
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