3-DIMENSIONAL STRUCTURE OF HUMAN LYSOSOMAL ASPARTYLGLUCOSAMINIDASE
3-DIMENSIONAL STRUCTURE OF HUMAN LYSOSOMAL ASPARTYLGLUCOSAMINIDASE
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DOI：
10.1038/nsb1295-1102
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发表时间：
1995-12-01
期刊：
影响因子：
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通讯作者：
PELTONEN, L
中科院分区：
文献类型：
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作者：
OINONEN, C;TIKKANEN, R;PELTONEN, L
人溶酶体天冬氨酸氨基葡萄糖苷酶(AGA)的高分辨晶体结构已被测定，这种溶酶体酶被合成为单一的多肽前体，翻译后立即切割成α和β亚基。发现两个α-链和β-链堆积在一起形成最终的异四聚体结构，即催化必需残基，β-链的N-末端苏氨酸位于漏斗状活性中心的深袋中。基于酶-产物复合体的结构，我们提出了这种溶酶体酶的催化机制，具有异常高的最适pH，三维结构还允许预测人类突变导致天冬氨酸氨基葡萄糖尿(ACU)的结构后果，天冬氨酸氨基葡萄糖尿症(ACU)是一种溶酶体储存性疾病。
The high resolution crystal structure of human lysosomal aspartylglucosaminidase (AGA) has been determined, This lysosomal enzyme is synthesized as a single polypeptide precursor, which is immediately post-translationally cleaved into alpha- and beta-subunits. Two alpha- and beta-chains are found to pack together forming the final heterotetrameric structure, The catalytically essential residue, the N-terminal threonine of the beta-chain is situated in the deep pocket of the funnel-shaped active site. On the basis of the structure of the enzyme-product complex we present a catalytic mechanism for this lysosomal enzyme with an exceptionally high pH optimum, The three-dimensional structure also allows the prediction of the structural consequences of human mutations resulting in aspartylglucosaminuria (ACU), a lysosomal storage disease.