3L4X

Crystal complex of N-terminal Human Maltase-Glucoamylase with NR4-8

Summary for 3L4X

• Entry DOI: 10.2210/pdb3l4x/pdb
• Related: 3L4T 3L4U 3L4V 3L4W 3L4Y 3L4Z
• Descriptor: Maltase-glucoamylase, intestinal, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, (1S,2R,3S,4S)-1-{(1S)-2-[(2R,3S,4S)-3,4-dihydroxy-2-(hydroxymethyl)tetrahydrothiophenium-1-yl]-1-hydroxyethyl}-2,3,4,5-tetrahydroxypentyl sulfate, ... (6 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: 100715.17

Authors

Sim, L.,Rose, D.R. (deposition date: 2009-12-21, release date: 2010-02-09, Last modification date: 2020-07-29)

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

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: 20039683
DOI: 10.1021/bi9016457

Experimental method

X-RAY DIFFRACTION (1.9 Å)