3L4T
Crystal complex of N-terminal Human Maltase-Glucoamylase with BJ2661
Summary for 3L4T
| Entry DOI | 10.2210/pdb3l4t/pdb |
| Related | 3L4U 3L4V 3L4W 3L4X 3L4Y 3L4Z |
| Descriptor | Maltase-glucoamylase, intestinal, (1R,2S)-1-[(1S)-1,2-dihydroxyethyl]-3-[(2R,3S,4S)-3,4-dihydroxy-2-(hydroxymethyl)tetrahydrothiophenium-1-yl]-2-hydroxypropyl sulfate, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (4 entities in total) |
| Functional Keywords | glycoside hydrolase family 31, cell membrane, disulfide bond, glycoprotein, glycosidase, hydrolase, membrane, multifunctional enzyme, polymorphism, signal-anchor, sulfation, transmembrane |
| Biological source | Homo sapiens (human) |
| Cellular location | Apical cell membrane; Single-pass type II membrane protein: O43451 |
| Total number of polymer chains | 1 |
| Total formula weight | 100083.55 |
| Authors | Sim, L.,Rose, D.R. (deposition date: 2009-12-21, release date: 2010-02-09, Last modification date: 2024-10-16) |
| Primary citation | Sim, L.,Jayakanthan, K.,Mohan, S.,Nasi, R.,Johnston, B.D.,Pinto, B.M.,Rose, D.R. New glucosidase inhibitors from an ayurvedic herbal treatment for type 2 diabetes: structures and inhibition of human intestinal maltase-glucoamylase with compounds from Salacia reticulata. Biochemistry, 49:443-451, 2010 Cited by PubMed Abstract: An approach to controlling blood glucose levels in individuals with type 2 diabetes is to target alpha-amylases and intestinal glucosidases using alpha-glucosidase inhibitors acarbose and miglitol. One of the intestinal glucosidases targeted is the N-terminal catalytic domain of maltase-glucoamylase (ntMGAM), one of the four intestinal glycoside hydrolase 31 enzyme activities responsible for the hydrolysis of terminal starch products into glucose. Here we present the X-ray crystallographic studies of ntMGAM in complex with a new class of alpha-glucosidase inhibitors derived from natural extracts of Salacia reticulata, a plant used traditionally in Ayuverdic medicine for the treatment of type 2 diabetes. Included in these extracts are the active compounds salacinol, kotalanol, and de-O-sulfonated kotalanol. This study reveals that de-O-sulfonated kotalanol is the most potent ntMGAM inhibitor reported to date (K(i) = 0.03 microM), some 2000-fold better than the compounds currently used in the clinic, and highlights the potential of the salacinol class of inhibitors as future drug candidates. PubMed: 20039683DOI: 10.1021/bi9016457 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.9 Å) |
Structure validation
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