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首页> 外文期刊>Biochemistry >Crystal Structures of Pasteurella multocida Sialyltransferase Complexes with Acceptor and Donor Analogues Reveal Substrate Binding Sites and Catalytic Mechanism
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Crystal Structures of Pasteurella multocida Sialyltransferase Complexes with Acceptor and Donor Analogues Reveal Substrate Binding Sites and Catalytic Mechanism

机译：Pasteurella Multiocada Sialyl转移酶复合物的晶体结构与受体和供体类似物显示底物结合位点和催化机制

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摘要

Sialyltransferases are key enzymes involved in the biosynthesis of biologically and pathologically important sialic acid-containing molecules in nature. Binary X-ray crystal structures of a multifunctional Pasteurella multocida sialyltransferase (DELTA24PmST1) with a donor analogue CMP-3F(a)Neu5Ac or CMP-3F(e)Neu5Ac were determined at 2.0 and 1.9 A resolutions, respectively. Ternary X-ray structures of the protein in complex with CMP or a donor analogue CMP-3F(a)Neu5 Ac and an acceptor lactose have been determined at 2.0 and 2.27 A resolutions, respectively. This represents the first sialyltransferase structure and the first GT-B-type glycosyltransferase structure that is bound to both a donor analogue and an acceptor simultaneously. The four structures presented here reveal that binding of the nucleotide-activated donor sugar causes a buried tryptophan to flip out of the protein core to interact with the donor sugar and helps define the acceptor sugar binding site. Additionally, key amino acid residues involved in the catalysis have been identified. Structural and kinetic data support a direct displacement mechanism involving an oxocarbenium ion-like transition state assisted with Asp141 serving as a general base to activate the acceptor hydroxyl group.
机译：Sialyl转移酶是在自然界中涉及生物学和病理上重要的唾液酸分子的生物合成的关键酶。用供体模拟CMP-3F（A）NEU5AC或CMP-3F（E）NEU5AC分辨率分辨率测定多功能巴豆菌多氨基甲烷转移酶（DELTA24PMST1）的二元X射线晶体结构。在2.0和2.27分辨率下分别测定了与CMP或供体类似物CMP-3F（A）NEU5 AC（A）NEU5 AC（A）NEU5 AC和受体乳糖的蛋白质的三元X射线结构。这代表了第一唾液酸三烷烃结构和第一GT-B型糖基转移酶结构，其与供体类似物和受体相结合。本文呈现的四种结构表明，核苷酸活化的供体糖的结合导致掩埋的色氨酸使得从蛋白质中翻出来与供体糖相互作用，并有助于定义受体糖结合位点。另外，已经鉴定了催化中涉及的关键氨基酸残基。结构和动力学数据支持一种涉及辅助亚太甘油的离子样过渡状态，辅助用作α1141用作活化羟基的一般碱。

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