Structure-function relationships of insect enzymes homologous to human glycan-related enzymes

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K15748
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 38030:Applied biochemistry-related
• Research Institution: Shizuoka University
• Principal Investigator: Miyazaki Takatsugu 静岡大学, グリーン科学技術研究所, 助教 (30775721)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 糖転移酵素 / 糖質加水分解酵素 / N結合型糖鎖 / O結合型糖鎖 / CAZy / 糖タンパク質 / X線結晶構造解析 / 昆虫

Outline of Final Research Achievements

This study focused on insect function-unknown proteins homologous to human glycosyltransferases and glycosidases involved in glycan biosynthesis and related enzymes. We identified and characterized Bombyx mori β-1,4-N-acetylgalactosaminyltransferase, a homolog of human β-1,4-galactosyltransferase, and also identified the C-terminal domain of human and B. mori glycosyltransferases as a new carbohydrate-binding module. B. mori α-fucosidase and α-N-acetylgalactosaminidase was revealed to have specificity towards N- and O-glycans, respectively. Moreover, we determined the crystal structures of two sucrose hydrolases from B. mori, α-1,2-mannosidase and α-N-acetylgalactosaminidase from Enterococcus faecalis acting on N- and O-glycans, respectively, α-1,2-glucosidase from Flavobacterium johnsoniae specific for kojibiose, and α-1,3-glucosidase from Lactococcus lactis specific for nigerose.

Free Research Field

酵素学

Academic Significance and Societal Importance of the Research Achievements

糖鎖はあらゆる生理機能や疾患、細菌やウイルスの感染に関与しているため、創薬・医療の観点からも重要な研究対象である。本研究においてヒトと昆虫の酵素活性と構造の違いを明らかにしたことから、昆虫細胞や虫体を用いたヒト型糖タンパク質生産の基盤構築に寄与するものと考えらえる。また、糖鎖およびその部分構造に高い特異性を持つ複数の酵素を発見し、その立体構造を明らかにしたことから、酵素を利用した糖鎖の加工技術の開発に応用できる可能性を示した。