Analysis of the biosynthetic mechanism and functions of glycosaminogycans by manipulating the genes encoding biosynthetic enzymes.

(1)首次证实人EXTL1和EXTL3具有参与硫酸肝素合成的糖基转移酶活性。(2)首次克隆人软骨素合成酶。(3)结果表明，除了人类EXT1和EXT2酶复合物外，受体核心蛋白片段可用于硫酸肝素聚合。(4)首次克隆到链式聚合所需的人软骨素聚合因子。(5)克隆了软骨素/皮肤素4- o -硫基转移酶，并对其底物特异性进行了详细的表征。(6)在杂化型蛋白聚糖syndecan-1的硫酸软骨素链中，发现gag -蛋白连接区四糖中的一个Gal残基在硫酸软骨素链中被硫酸化，而在硫酸肝素链中没有被硫酸化。(7)首次证实了具有GlcNAc转移酶活性的EXTL2的晶体结构。(8)软骨蛋白在秀丽隐杆线虫胚胎细胞分裂中起重要作用。

(1) Human EXTL1 and EXTL3 were demonstrated for the first time to exhibit glycosyltransferase activities involved in heparan sulfate synthesis.(2) Human chondrotiin synthase was cloned for the first time.(3) It was demonstrated that acceptor core protein moieties in addition to an enzyme complex of human EXT1 and EXT2 for heparan sulfate polymerization.(4) Human chondroitin polymerizing factor required for chain polymerization of chondroitin was cloned for the first time.(5) Chondroitin/dermatan 4-O-sulfotransferases were cloned and their detailed substrate specificity was characterized.(6) It was found that one of the Gal residues in the GAG-protein linkage region tetrasaccharide is sulfated in the chondroitin sulfate chains but not in the heparan sulfate chains of a hybrid type proteoglycan syndecan-1.(7) The crystal structure of EXTL2, which exhibits GlcNAc transferase activity, was demonstrated for the first time.(8) Choncdoirin was demonstrated to be essential for the embryonic cell division of C.elegans.