3TOP

Crystral Structure of the C-terminal Subunit of Human Maltase-Glucoamylase in Complex with Acarbose

Summary for 3TOP

• Entry DOI: 10.2210/pdb3top/pdb
• Related: 3TON
• Related PRD ID: PRD_900007
• Descriptor: Maltase-glucoamylase, intestinal, 4,6-dideoxy-4-{[(1S,4R,5S,6S)-4,5,6-trihydroxy-3-(hydroxymethyl)cyclohex-2-en-1-yl]amino}-alpha-D-glucopyranose-(1-4)-alpha-D-glucopyranose-(1-4)-alpha-D-glucopyranose (3 entities in total)
• Functional Keywords: membrane, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: Homo sapiens (human)
• Cellular location: Apical cell membrane; Single-pass type II membrane protein: O43451
• Total number of polymer chains: 2
• Total formula weight: 208745.59

Authors

Shen, Y.,Qin, X.H.,Ren, L.M. (deposition date: 2011-09-06, release date: 2011-11-23, Last modification date: 2024-11-06)

Primary citation

Ren, L.M.,Qin, X.H.,Cao, X.F.,Wang, L.L.,Bai, F.,Bai, G.,Shen, Y.
Structural insight into substrate specificity of human intestinal maltase-glucoamylase
Protein Cell, 2:827-836, 2011

PubMed Abstract: Human maltase-glucoamylase (MGAM) hydrolyzes linear alpha-1,4-linked oligosaccharide substrates, playing a crucial role in the production of glucose in the human lumen and acting as an efficient drug target for type 2 diabetes and obesity. The amino- and carboxyl-terminal portions of MGAM (MGAM-N and MGAM-C) carry out the same catalytic reaction but have different substrate specificities. In this study, we report crystal structures of MGAM-C alone at a resolution of 3.1 Å, and in complex with its inhibitor acarbose at a resolution of 2.9 Å. Structural studies, combined with biochemical analysis, revealed that a segment of 21 amino acids in the active site of MGAM-C forms additional sugar subsites (+ 2 and + 3 subsites), accounting for the preference for longer substrates of MAGM-C compared with that of MGAM-N. Moreover, we discovered that a single mutation of Trp1251 to tyrosine in MGAM-C imparts a novel catalytic ability to digest branched alpha-1,6-linked oligosaccharides. These results provide important information for understanding the substrate specificity of alpha-glucosidases during the process of terminal starch digestion, and for designing more efficient drugs to control type 2 diabetes or obesity.

PubMed: 22058037
DOI: 10.1007/s13238-011-1105-3

Experimental method

X-RAY DIFFRACTION (2.881 Å)