O-糖基化起始糖基转移酶的活性与结构研究

多肽：N-乙酰氨基半乳糖转移酶（ppGalNAc-T） 是催化N-乙酰氨基半乳糖（GalNAc）结合到蛋白质Ser或Thr上的糖基转移酶，是黏蛋白型O-糖基化修饰的起始糖基转移酶。ppGalNAc-T是一个酶家族，表达产物均为Ⅱ型膜蛋白。虽然氨基酸序列高度同源，但各成员具有独特的底物特异性和动力学特征。因此，ppGalNAc-T的底物作用机制是O-糖基化研究领域中的关键课题。近年来，通过利用定点突变及晶体结构解析技术，ppGalNAc-T中与底物相互作用的重要氨基酸残基以及由这些残基所形成的对底物结合起关键作用的空间构象逐渐被揭示，为了解ppGalNAc-T酶家族的底物作用机制及其蛋白结构与催化活性间的关系提供了理论依据。

Catalytic activity and structure analysis of the initial glycosyltransferase of O-glycosylation

Mucin-type O-glycosylation is iniPtiated by members of the UDP-GalNAc： polypeptide N-acetylgalactos aminyltransferase （ppGalNAc-T） family which transfers the GalNAc residue to the Ser or Thr of target proteins. ppGalNAc-Ts are type II membrane proteins. Although ppGalNAc-Ts are highly homologous in their amino acid sequences, each member has unique substrate preference and dynamic properties. Thus, the mechanism of enzyme- substrates interaction is an essential issue in O-glycosylation research. Recently, the crucial amino acid residues which bind with substrates and the enzymatic conformation formed by these residues have been revealed by sitedirected mutagenesis and crystal structure analysis. These investigations provide an important basis for better understanding of the mechanism of enzyme-substrate interaction as well as the structure-function relationship of the ppGalNAc-T family.