血糖生成酵素MGAMの分子構造と阻害機構を解明～血糖値上昇を抑制する新規薬剤・食品開発への貢献に期待～

2026-02-06 北海道大学,高エネルギー加速器研究機構,筑波大学

クライオ電子顕微鏡-単粒子解析によって明らかにしたブタ血清MGAMと拮抗阻害剤AC5との複合体構造。AC5(青と赤)はMGAMのNtMGAMユニット(黄色)とCtMGAMユニット(ピンク)それぞれの活性部位に結合する「二重の拮抗阻害剤」として働くため、阻害型式は一見すると混合阻害として観測されることが明らかとなった。

<関連情報>

• https://www.hokudai.ac.jp/news/2026/02/mgam.html
• https://www.hokudai.ac.jp/news/pdf/260206_pr.pdf
• https://www.tandfonline.com/doi/full/10.1080/14756366.2025.2612391

ブタ血清マルターゼ-グルコアミラーゼ:立体構造、反応動態並びに阻害 Porcine serum maltase-glucoamylase: structure, kinetics, and inhibition

Ken Watanabe,Takayoshi Tagami,Chihiro Biwa,Masato Kawasaki,Naruhiko Adachi,Toshio Moriya, …
Journal of Enzyme Inhibition and Medicinal Chemistry  Published:14 Jan 2026
DOI:https://doi.org/10.1080/14756366.2025.2612391

Abstract

Maltase-glucoamylase (MGAM) is a small-intestinal enzyme comprising two tandem α-glucosidase units, NtMGAM and CtMGAM, each capable of hydrolysing maltodextrins into glucose. MGAM serves as a therapeutic target for managing postprandial hyperglycaemia; comprehensive insights into its full-length three-dimensional structure and inhibitor kinetics remains limited. Here, we demonstrate that the α-glucosidase in porcine serum is comparable to that encoded by the MGAM gene. Using cryo-electron microscopy, we determined the complex structure of serum MGAM with the inhibitor acarviosyl-maltotriose (AC5), which was found to bind exclusively to the active sites of each unit, confirming the presence of independent catalytic sites. AC5 was shown to exhibit mixed-type inhibition towards full-length serum MGAM and competitive inhibition against both recombinant NtMGAM and CtMGAM. The apparent mixed-type inhibition can be more accurately attributed to dual competitive inhibition mechanisms. These findings contribute to the advancement of functional foods and therapeutic interventions for postprandial hyperglycaemia and type 2 diabetes.