Mechanistic insights into a Ca2+-dependent family of alpha-mannosidases in a human gut symbiont.
Mechanistic insights into a Ca2+-dependent family of alpha-mannosidases in a human gut symbiont.
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DOI：
10.1038/nchembio.278
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发表时间：
2010-02
影响因子：
14.8
通讯作者：
Davies GJ
中科院分区：
文献类型：
--
作者：
Zhu Y;Suits MD;Thompson AJ;Chavan S;Dinev Z;Dumon C;Smith N;Moremen KW;Xiang Y;Siriwardena A;Williams SJ;Gilbert HJ;Davies GJ
以多形拟杆菌（Bacteroides thetaiotaomicron）为例的结肠细菌通过利用糖苷水解酶（GH）的大家族来利用膳食多糖和宿主聚糖作为营养素，在维持人类健康方面发挥关键作用。这种GH家族扩展的例子是由B编码的23种家族GH 92糖苷酶。多形核基因组。在这里，我们表明，这些是α-甘露聚糖酶，通过一个单一的位移机制，以利用主机N-聚糖。两个GH 92甘露聚糖酶的三维结构定义了一个双结构域蛋白家族，其中催化中心位于结构域界面，以Ca 2+依赖的方式为水解提供酸（谷氨酸）和碱（天冬氨酸）帮助。与抑制剂复合的GH 92的三维结构提供了对催化的特异性、机制和构象路线的深入了解。Ca 2+在帮助甘露糖苷从基态4C 1椅式构象向过渡态扭曲中起着关键的催化作用。
Colonic bacteria, exemplified by Bacteroides thetaiotaomicron, play a key role in maintaining human health by harnessing large families of glycoside hydrolases (GHs) to exploit dietary polysaccharides and host glycans as nutrients. Such GH family expansion is exemplified by the 23 family GH92 glycosidases encoded by the B. thetaiotaomicron genome. Here we show that these are α-mannosidases that act via a single displacement mechanism to utilize host N-glycans. The three-dimensional structure of two GH92 mannosidases defines a family of two-domain proteins in which the catalytic center is located at the domain interface, providing acid (glutamate) and base (aspartate) assistance to hydrolysis in a Ca2+-dependent manner. The three-dimensional structures of the GH92s in complex with inhibitors provide insight into the specificity, mechanism and conformational itinerary of catalysis. Ca2+ plays a key catalytic role in helping distort the mannoside away from its ground-state 4C1 chair conformation toward the transition state.
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影响因子：
3.9
作者：
Davies, GJ;Ducros, VMA;Zechel, DL
通讯作者：
Zechel, DL
影响因子：
5.7
作者：
Nurizzo, D;Nagy, T;Davies, GJ
通讯作者：
Davies, GJ
影响因子：
30.3
作者：
Martens EC;Chiang HC;Gordon JI
通讯作者：
Gordon JI
DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
Emsley, P;Cowtan, K
通讯作者：
Cowtan, K
影响因子：
56.9
作者：
Gill, Steven R.;Pop, Mihai;Nelson, Karen E.
通讯作者：
Nelson, Karen E.