Structural basis for arginine glycosylation of host substrates by bacterial effector proteins.
Structural basis for arginine glycosylation of host substrates by bacterial effector proteins.
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DOI：
10.1038/s41467-018-06680-6
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发表时间：
2018-10-16
影响因子：
16.6
通讯作者：
Cho HS
中科院分区：
文献类型：
--
作者：
Park JB;Kim YH;Yoo Y;Kim J;Jun SH;Cho JW;El Qaidi S;Walpole S;Monaco S;García-García AA;Wu M;Hays MP;Hurtado-Guerrero R;Angulo J;Hardwidge PR;Shin JS;Cho HS
细菌效应蛋白SseK和NleB在精氨酸残基上糖基化宿主蛋白，导致对感染的NF-κ B依赖性应答降低。沙门氏菌SseK 1和SseK 2为E. coli NleB 1直系同源物，表现为NleB 1样GT，尽管它们在蛋白底物特异性上不同。在这里，我们报告说，这些酶保留糖基转移酶组成的螺旋-环-螺旋（HLH）结构域，盖结构域，和催化结构域。HEN活性位点的保守基序（His-Glu-Asn）对酶催化和细菌毒力具有重要作用。我们观察SseK 1和SseK 2之间的差异，在与底物的相互作用，并确定底物残基是关键的酶识别。长分子动力学模拟表明，HLH结构域决定底物特异性和盖结构域调节活性位点的开放。总的来说，我们的数据表明了一个正面SNi机制，解释了这些效应物之间的活性差异，并对未来针对肠道病原体的药物开发产生了影响。III型分泌系统效应物NleB和SseK是特异性糖基化精氨酸残基的糖基转移酶（GT）。在本文中，作者通过结合X射线晶体学、NMR、酶动力学测量、分子动力学模拟和体内实验来深入了解它们的机制，并表明SseK/NleB酶保留了GT。
The bacterial effector proteins SseK and NleB glycosylate host proteins on arginine residues, leading to reduced NF-κB-dependent responses to infection. Salmonella SseK1 and SseK2 are E. coli NleB1 orthologs that behave as NleB1-like GTs, although they differ in protein substrate specificity. Here we report that these enzymes are retaining glycosyltransferases composed of a helix-loop-helix (HLH) domain, a lid domain, and a catalytic domain. A conserved HEN motif (His-Glu-Asn) in the active site is important for enzyme catalysis and bacterial virulence. We observe differences between SseK1 and SseK2 in interactions with substrates and identify substrate residues that are critical for enzyme recognition. Long Molecular Dynamics simulations suggest that the HLH domain determines substrate specificity and the lid-domain regulates the opening of the active site. Overall, our data suggest a front-face SNi mechanism, explain differences in activities among these effectors, and have implications for future drug development against enteric pathogens. The type III secretion system effectors NleB and SseK are glycosyltransferases (GT) that specifically glycosylate arginine residues. Here the authors provide insights into their mechanism by combining X-ray crystallography, NMR, enzyme kinetics measurements, molecular dynamics simulations and in vivo experiments and show that SseK/NleB enzymes are retaining GTs.
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影响因子：
30.3
作者：
Gao X;Wang X;Pham TH;Feuerbacher LA;Lubos ML;Huang M;Olsen R;Mushegian A;Slawson C;Hardwidge PR
通讯作者：
Hardwidge PR
影响因子：
2.9
作者：
Jacobson, MP;Pincus, DL;Friesner, RA
通讯作者：
Friesner, RA
DOI：
10.1073/pnas.1113921108
发表时间：
2011-12-27
影响因子：
11.1
作者：
Chaikuad, Apirat;Froese, D. Sean;Yue, Wyatt W.
通讯作者：
Yue, Wyatt W.
DOI：
10.1038/nrmicro2199
发表时间：
2009-09
期刊：
Nature reviews. Microbiology
影响因子：
--
作者：
通讯作者：
--
影响因子：
2
作者：
Castanar, Laura;Sistare, Eduard;Parella, Teodor
通讯作者：
Parella, Teodor