Structure, Function and Mechanism of N-Glycan Processing Enzymes: endo -a-1,2-Mannanase and endo -a-1,2-Mannosidase
Structure, Function and Mechanism of N-Glycan Processing Enzymes: endo -a-1,2-Mannanase and endo -a-1,2-Mannosidase
复制标题
N-聚糖加工酶的结构、功能和机制：内切-a-1,2-甘露聚糖酶和内切-a-1,2-甘露糖苷酶
DOI：
10.1002/ijch.202200067
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发表时间：
2022
影响因子：
3.2
通讯作者：
Burchill L
中科院分区：
文献类型：
--
作者：
Burchill L
虽然大多数作用于N-连接聚糖的糖苷酶一次去除单个糖残基，但糖苷水解酶家族GH 99的内切-α-1，2-甘露糖苷酶和内切-α-1，2-甘露聚糖酶在链内切割并去除两个或更多个糖残基。它们是使用涉及环氧化物中间体的酶机制的立体化学保留酶。人内-α-1，2-甘露糖苷酶（MANEA）修剪葡萄糖基化甘露糖残基;内甘露糖苷酶途径为糖蛋白成熟提供了一种葡萄糖苷酶非依赖性途径。细胞活性MANEA抑制剂改变N-聚糖加工并降低登革病毒的感染性，表明MANEA具有作为宿主定向抗病毒靶点的潜力。来自肠道拟杆菌属的序列相关酶显示出tendo-α-1，2-甘露糖苷酶活性，是结构导向抑制剂开发的富有成效的试验平台。拟杆菌属（Bacteroidesspp.）酶位于多糖利用位点内，并且是优选的内切-α-1，2-甘露聚糖酶。
While most glycosidases that act on N‐linked glycans remove a single sugar residue at a time,endo‐α‐1,2‐mannosidases andendo‐α‐1,2‐mannanases of glycoside hydrolase family GH99 cut within a chain and remove two or more sugar residues. They are stereochemically retaining enzymes that use an enzymatic mechanism involving an epoxide intermediate. Humanendo‐α‐1,2‐mannosidase (MANEA) trims glucosylated mannose residues; the endomannosidase pathway provides a glucosidase‐independent pathway for glycoprotein maturation. Cell‐active MANEA inhibitors alter N‐glycan processing and reduce infectivity of dengue virus, demonstrating that MANEA has potential as a host‐directed antiviral target. Sequence‐related enzymes from gutBacteroidesspp. exhibitendo‐α‐1,2‐mannosidase activity and are a fruitful test bed for structure‐guided inhibitor development. The genes encoding theBacteroidesspp. enzymes sit within polysaccharide utilization loci and are preferentialendo‐α‐1,2‐mannanases.