Tews I, Perrakis A, Oppenheim A, Dauter Z, Wilson K S, Vorgias C E
European Molecular Biology Laboratory, Hamburg, Germany.
Nat Struct Biol. 1996 Jul;3(7):638-48. doi: 10.1038/nsb0796-638.
Chitin, the second most abundant polysaccharide on earth, is degraded by chitinases and chitobiases. The structure of Serratia marcescens chitobiase has been refined at 1.9 A resolution. The mature protein is folded into four domains and its active site is situated at the C-terminal end of the central (beta alpha)8-barrel. Based on the structure of the complex with the substrate disaccharide chitobiose, we propose an acid-base reaction mechanism, in which only one protein carboxylate acts as catalytic acid, while the nucleophile is the polar acetamido group of the sugar in a substrate-assisted reaction. The structural data lead to the hypothesis that the reaction proceeds with retention of anomeric configuration. The structure allows us to model the catalytic domain of the homologous hexosaminidases to give a structural rationale to pathogenic mutations that underlie Tay-Sachs and Sandhoff disease.
几丁质是地球上第二丰富的多糖，可被几丁质酶和壳二糖酶降解。粘质沙雷氏菌壳二糖酶的结构已在1.9埃分辨率下得到优化。成熟蛋白折叠成四个结构域，其活性位点位于中央（β-α）8桶的C末端。基于与底物二糖壳二糖形成的复合物的结构，我们提出了一种酸碱反应机制，其中只有一个蛋白质羧酸盐作为催化酸，而亲核试剂是底物辅助反应中糖的极性乙酰氨基基团。结构数据导致这样的假设，即反应以异头构型的保留进行。该结构使我们能够对同源己糖胺酶的催化结构域进行建模，从而为泰-萨克斯病和桑德霍夫病的致病突变提供结构依据。
