Structural studies on meta-stable conformations of bisected glycan

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K07303
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Structural biochemistry
• Research Institution: Osaka University (2019); The University of Tokyo (2017-2018)
• Principal Investigator: Nagae Masamichi 大阪大学, 微生物病研究所, 助教 (60619873)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 構造生物学 / 糖鎖生物学

Outline of Final Research Achievements

Polysaccharides are composed of various monosaccharide residues linked with glycosidic bonds. The 3D structures of polysaccharide are supposed to exist as dynamic equilibrium of multiple conformations. Compared with nucleic acids and proteins, the investigation of the relationship between sequence and 3D structure of polysaccharide has been not fully understood yet. This is because of high flexibility of 3D structure of polysaccharide and technical difficulties of structural analyses. In this proposal, I proposed the structural analysis of N-glycan which is representative glycan in mammals by X-ray crystallography. I and co-workers clarified several atomic structures of N-glycan and its related glycoproteins in this three years. Especially, we reported the crystal structure of cancer-associated glycosyltransferase GnT-V in complex with ligand N-glycan. This report has the potential to clarify the relationship between cancer specific glycan and its behavior.

Free Research Field

構造生物化学

Academic Significance and Societal Importance of the Research Achievements

糖鎖の配列と構造の相関は生体高分子に関する基礎研究であり、一見すると社会的な成果の還元が難しいように思われるかもしれない。しかし我々の体の中には数百種類の糖転移酵素が常時働いており、複雑な化学構造を持つ糖鎖が数多く存在する。驚くべきことにこれらの糖鎖の生理学的な意義は未だ不明な点だらけである。私の研究は生体内に豊富に存在するN型糖鎖に焦点を当て、その糖鎖の構造および改変メカニズムを形の情報から明らかにすることを目的にしていた。今回の研究を通してがん悪性化に関与する糖転移酵素の立体構造を明らかにすることができた。この成果は将来的な糖鎖の機能の解明につながることが期待される。