Protein & Cell

, Volume 2, Issue 10, pp 827–836 | Cite as

Structural insight into substrate specificity of human intestinal maltase-glucoamylase

  • Limei Ren
  • Xiaohong Qin
  • Xiaofang Cao
  • Lele Wang
  • Fang Bai
  • Gang BaiEmail author
  • Yuequan ShenEmail author
Research Article


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 alphaglucosidases during the process of terminal starch digestion, and for designing more efficient drugs to control type 2 diabetes or obesity.


MGAM C-terminal domain inhibitor crystal structure acarbose type 2 diabetes 

Supplementary material

13238_2011_1105_MOESM1_ESM.pdf (372 kb)
Supplementary material, approximately 372 KB.


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Copyright information

© Higher Education Press and Springer-Verlag Berlin Heidelberg 2011

Authors and Affiliations

  1. 1.State Key Laboratory of Medicinal Chemical BiologyNankai UniversityTianjinChina
  2. 2.College of PharmacyNankai UniversityTianjinChina
  3. 3.College of Life SciencesNankai UniversityTianjinChina

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