tailieunhanh - Báo cáo khoa học: Inhibition of recombinant human maltase glucoamylase by salacinol and derivatives

Inhibitors targeting pancreatic a-amylase and intestinal a-glucosidases delay glucose production following digestion and are currently used in the treatment of Type II diabetes. Maltase-glucoamylase (MGA), a family 31 glycoside hydrolase, is ana-glucosidase anchored in the membrane of small intestinal epithelial cells responsible for the final step of mammalian starch digestion leading to the release of glucose. | ềFEBS Journal Inhibition of recombinant human maltase glucoamylase by salacinol and derivatives Elena J. Rossi1 2 Lyann Sim1 2 z Douglas A. Kuntz2 Dagmar Hahn3 Blair D. Johnston4 Ahmad Ghavami4 Monica G. Szczepina4 Nag S. Kumar4 Erwin E. Sterchi3 Buford L. Nichols5 B. M. Pinto4 and David R. Rose1 2 1 Department of MedicalBiophysics University of Toronto Canada 2 Division of Cancer Genomics and Proteomics Ontario Cancer Institute Canada 3 Institute of Biochemistry and Molecular Medicine University of Berne Switzerland 4 Department of Chemistry Simon Fraser University Burnaby Canada 5 US Department of Agriculture AgriculturalResearch Service Baylor College of Medicine Houston TX USA Keywords enzyme inhibition family GH31 glucosidase glycosyl hydrolase salacinol Correspondence D. R. Rose Ontario Cancer Institute 101 College Street Toronto ON M5G 1L7 Canada Fax 416 581 7562 Tel 416 581 7537 Email drose@ http These authors contributed equally to this work Received 5 January 2006 revised 11 April 2006 accepted 13 April 2006 doi Inhibitors targeting pancreatic a-amylase and intestinal a-glucosidases delay glucose production following digestion and are currently used in the treatment of Type II diabetes. Maltase-glucoamylase MGA a family 31 glycoside hydrolase is an a-glucosidase anchored in the membrane of small intestinal epithelial cells responsible for the final step of mammalian starch digestion leading to the release of glucose. This paper reports the production and purification of active human recombinant MGA amino terminal catalytic domain MGAnt from two different eukaryotic cell culture systems. MGAnt overexpressed in Drosophila cells was of quality and quantity suitable for kinetic and inhibition studies as well as future structural studies. Inhibition of MGAnt was tested with a group of prospective a-glucosi-dase inhibitors modeled after salacinol a naturally occurring a-glucosidase inhibitor and