N-glycosylation of enhanced aromatic sequons to increase glycoprotein stability.
N-glycosylation of enhanced aromatic sequons to increase glycoprotein stability.
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DOI：
10.1002/bip.22030
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发表时间：
2012
期刊：
影响因子：
2.9
通讯作者：
Kelly, Jeffery W.
中科院分区：
文献类型：
--
作者：
Price, Joshua L.;Culyba, Elizabeth K.;Chen, Wentao;Murray, Amber N.;Hanson, Sarah R.;Wong, Chi-Huey;Powers, Evan T.;Kelly, Jeffery W.
N -糖基化可提高蛋白质折叠速率，增强热力学稳定性，并减缓蛋白质去折叠；然而，这些效应的分子基础尚未完全了解。由于缺乏明确的工程指导原则，将N -糖基化用作稳定蛋白质的方法的尝试导致了不可预测的能量学后果。在此，我们综述了三种“增强型芳香族序列子”的最新进展，当置于适当的回折结构环境中时，它们似乎有助于稳定苯丙氨酸、天冬酰胺 - N -乙酰葡糖胺和苏氨酸之间的天然态相互作用。事实证明，将一种稳定的增强型芳香族序列子工程化引入未进化出优化特定蛋白质 - 碳水化合物相互作用的非糖基化蛋白质是简单直接的。将这些增强型芳香族序列子整合到蛋白质内适当的回折类型中，应可通过减少未折叠的易被蛋白酶水解以及易错误折叠形成聚集体的状态，增强基于N -糖基化稳定作用的众所周知的药代动力学优势，从而使此类蛋白质在研究和制药应用中更有用。
N-glycosylation can increase the rate of protein folding, enhance thermodynamic stability, and slow protein unfolding; however, the molecular basis for these effects is incompletely understood. Without clear engineering guidelines, attempts to use N-glycosylation as an approach for stabilizing proteins have resulted in unpredictable energetic consequences. Here we review the recent development of three “enhanced aromatic sequons”, which appear to facilitate stabilizing native-state interactions between Phe, Asn-GlcNAc and Thr when placed in an appropriate reverse turn context. It has proven to be straightforward to engineer a stabilizing enhanced aromatic sequon into glycosylation-naïve proteins that have not evolved to optimize specific protein-carbohydrate interactions. Incorporating these enhanced aromatic sequons into appropriate reverse turn types within proteins should enhance the well-known pharmacokinetic benefits of N-glycosylation-based stabilization by lowering the population of unfolded protease-susceptible and misfolded aggregation-prone states, thereby making such proteins more useful in research and pharmaceutical applications.
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DOI：
10.1126/science.1198461
发表时间：
2011-02-04
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Culyba EK;Price JL;Hanson SR;Dhar A;Wong CH;Gruebele M;Powers ET;Kelly JW
通讯作者：
Kelly JW
影响因子：
3.9
作者：
Ceaglio, N.;Etcheverrigaray, M.;Oggero, A.
通讯作者：
Oggero, A.
DOI：
10.1107/s0907444902003359
发表时间：
2002-05-01
期刊：
ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY
影响因子：
--
作者：
Hovmöller, S;Zhou, T;Ohlson, T
通讯作者：
Ohlson, T
影响因子：
5.7
作者：
BODIAN, DL;JONES, EY;DAVIS, SJ
通讯作者：
DAVIS, SJ
影响因子：
15
作者：
Hackenberger, CPR;Friel, CT;Imperiali, B
通讯作者：
Imperiali, B