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首页> 外文期刊>Acta crystallographica.Section D. Biological crystallography >The structure of human -2,6-sialyltransferase reveals the binding mode of complex glycans
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The structure of human -2,6-sialyltransferase reveals the binding mode of complex glycans

机译：人类的结构2,6-sialyltransferase揭示了复杂的绑定模式聚糖

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摘要

Human β-galactoside -2,6-sialyltransferase I (ST6Gal-I) establishes the final glycosylation pattern of many glycoproteins by transferring a sialyl moiety to a terminal galactose. Complete sialylation of therapeutic immunoglobulins is essential for their anti-inflammatory activity and protein stability, but is difficult to achieve in vitro owing to the limited activity of ST6Gal-I towards some galactose acceptors. No structural information on ST6Gal-I that could help to improve the enzymatic properties of ST6Gal-I for biotechnological purposes is currently available. Here, the crystal structures of human ST6Gal-I in complex with the product cytidine 5′-monophosphate and in complex with cytidine and phosphate are described. These complexes allow the rationalization of the inhibitory activity of cytosine-based nucleotides. ST6Gal-I adopts a variant of the canonical glycosyltransferase A fold and differs from related sialyltransferases by several large insertions and deletions that determine its regiospecificity and substrate specificity. A large glycan from a symmetry mate localizes to the active site of ST6Gal-I in an orientation compatible with catalysis. The glycan binding mode can be generalized to any glycoprotein that is a substrate of ST6Gal-I. Comparison with a bacterial sialyltransferase in complex with a modified sialyl donor lends insight into the Michaelis complex. The results support an SN2 mechanism with inversion of configuration at the sialyl residue and suggest substrate-assisted catalysis with a charge-relay mechanism that bears a conceptual similarity to serine proteases.
机译：人类β半乳糖苷2,6-sialyltransferase我(ST6Gal-I)建立最终的糖基化许多糖蛋白通过转移的模式sialyl一部分终端半乳糖。sialylation治疗免疫球蛋白重要的抗炎活性和蛋白质的稳定性,但很难实现体外由于有限的活动ST6Gal-I向一些半乳糖受体。结构性ST6Gal-I可能的信息有助于改善酶的性质ST6Gal-I用于生物技术目前可用的。人类ST6Gal-I在复杂的产品胞嘧啶核苷5 '一磷酸和复杂胞嘧啶核苷和磷酸盐。复合物允许的合理化抑制活性cytosine-based核苷酸。规范糖基转移酶折叠和不同由几家大型sialyltransferases有关确定它的插入和删除regiospecificity和底物特异性。从对称伙伴本地化大型多糖ST6Gal-I活性部位的一个方向与催化兼容。模式可以推广到任何糖蛋白是一个ST6Gal-I衬底。细菌sialyltransferase在复杂修改sialyl捐赠给洞察米歇利斯复杂。与反演的配置机制并建议substrate-assisted sialyl残渣催化charge-relay机制丝氨酸概念相似蛋白酶。

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