Structural and functional studies on the novel hyaluronidase trying for its clinical application

2014 Fiscal Year Final Research Report

• Project/Area Number: 24590071
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Biological pharmacy
• Research Institution: Meijo University
• Principal Investigator: YAMADA Shuhei 名城大学, 薬学部, 教授 (70240017)
• Co-Investigator(Renkei-kenkyūsha): SUGAHARA Kazuyuki 北海道大学, 先端生命科学研究院, 名誉教授 (60154449) ; YAMASHITA Tadashi 麻布大学, 獣医学部, 教授 (30220338) ; MIZUMOTO Shuji 名城大学, 薬学部, 助教 (40443973)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: コンドロイチン硫酸 / ヒアルロニダーゼ / 加水分解酵素 / ヒアルロン酸 / グリコサミノグリカン / 基質特異性

Outline of Final Research Achievements

The aim of this study was to characterize the amino acid residues responsible for the substrate specificity as well as to elucidate the biological functions of hyaluronidase 4 (HYAL4), which is a chondroitin sulfate-specific hydrolase. A series of HYAL4/other hyaluronidases-chimeric proteins and HYAL4 point mutants have been generated, and their preference for substrates has been investigated. The amino acid residues required for the substrate specificity of HYAL4 have been identified. The expression patterns as well as periods of HYAL4 mRNA have also been analyzed in detail. The relation between some diseases and HYAL4 has been investigated, and high expression of HYAL4 in some metastatic cancer cell lines has been demonstrated. We have also succeeded in the preparation of the targeting vector for generation of Hyal4-deficient mice.

Free Research Field

糖鎖生物学