Mechanism of sugar chain elongation catalyzed by muscular dystrophy cause gene product LARGE

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K07935
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Biological pharmacy
• Research Institution: Nagoya City University
• Principal Investigator: Yagi Hirokazu 名古屋市立大学, 大学院薬学研究科, 講師 (70565423)
• Co-Investigator(Renkei-kenkyūsha): KATO Koichi 名古屋市立大学, 大学院薬学研究科, 教授 (20211849) ; SUGIYAMA Masaaki 京都大学, 複合原子力科学研究所, 教授 (10253395) ; SATOH Tadashi 名古屋市立大学, 大学院薬学研究科, 准教授 (80532100) ; YAMAGUCHI Takumi 北陸先端科学技術大学院大学, マテリアルサイエンス系, 准教授 (60522430)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: LARGE / K4CP / 糖転移酵素 / 高速AFM

Outline of Final Research Achievements

LARGE (Like-acetylglucosaminyltransferase) is the causative gene product for congenital muscular dystrophy which possesses two catalytic domains with homology to members of glycosyltransferases to form a repeat sequence of xylose and glucuronic acid residues. In this study, we have performed a molecular dynamics study to characterize the mechanism that the enzymes composed of these two catalytic domains catalyze the elongation reactions of sugar chains. As a result, the enzymes exhibited dynamic motions involving domain-domain association and dissociation during the reaction, indicating that orientation between the two domains would contribute to the elongation efficiency to exchange the substrate sugar chain.

Free Research Field

糖鎖生化学