Mechanism of the Escherichia coli MltE lytic transglycosylase, the cell-wall-penetrating enzyme for Type VI secretion system assembly.
Mechanism of the Escherichia coli MltE lytic transglycosylase, the cell-wall-penetrating enzyme for Type VI secretion system assembly.
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DOI：
10.1038/s41598-018-22527-y
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发表时间：
2018-03-07
影响因子：
4.6
通讯作者：
Mobashery S
中科院分区：
文献类型：
--
作者：
Byun B;Mahasenan KV;Dik DA;Marous DR;Speri E;Kumarasiri M;Fisher JF;Hermoso JA;Mobashery S
裂解转糖基酶(LTS)通过分子内转缩醛反应催化细菌细胞壁的非水解性裂解。这种反应在细菌细胞壁的生物合成、循环、毒力的表现、鞭毛和菌毛等结构实体的插入等过程中具有关键和广泛的重要作用。首次对LT的反应机理进行了QM/MM分析，即对大肠杆菌MltE的反应机理进行了分析。这项研究揭示了一个构象路线，它符合类氧碳正离子的过渡态，其特征是活性中心谷氨酸在质子转移中起着关键作用。值得注意的是，作为潜在中间体的恶唑烷中间体是不存在的。相反，底物辅助催化是通过MurNac糖的N-乙酰基羰基提供的有利偶极来观察到的。这种相互作用使过渡态的初始正电荷发展趋于稳定。这一机制与缩醛裂解和缩醛形成的近同步过程相吻合。
Lytic transglycosylases (LTs) catalyze the non-hydrolytic cleavage of the bacterial cell wall by an intramolecular transacetalization reaction. This reaction is critically and broadly important in modifications of the bacterial cell wall in the course of its biosynthesis, recycling, manifestation of virulence, insertion of structural entities such as the flagellum and the pili, among others. The first QM/MM analysis of the mechanism of reaction of an LT, that for the Escherichia coli MltE, is undertaken. The study reveals a conformational itinerary consistent with an oxocarbenium-like transition state, characterized by a pivotal role for the active-site glutamic acid in proton transfer. Notably, an oxazolinium intermediate, as a potential intermediate, is absent. Rather, substrate-assisted catalysis is observed through a favorable dipole provided by the N-acetyl carbonyl group of MurNAc saccharide. This interaction stabilizes the incipient positive charge development in the transition state. This mechanism coincides with near-synchronous acetal cleavage and acetal formation.
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影响因子：
3.2
作者：
Kraft, AR;Templin, MF;Höltje, JV
通讯作者：
Höltje, JV
影响因子：
3.3
作者：
Jitonnom, Jitrayut;Limb, Michael A. L.;Mulholland, Adrian J.
通讯作者：
Mulholland, Adrian J.
影响因子：
3.5
作者：
Reid, Christopher W.;Legaree, Blaine A.;Clarke, Anthony J.
通讯作者：
Clarke, Anthony J.
影响因子：
6.8
作者：
Speciale, Gaetano;Thompson, Andrew J.;Davies, Gideon J.;Williams, Spencer J.
通讯作者：
Williams, Spencer J.
影响因子：
2.9
作者：
Çetinbas, N;Macauley, MS;Vocadlo, DJ
通讯作者：
Vocadlo, DJ