Deamidation of Protonated Asparagine-Valine Investigated by a Combined Spectroscopic, Guided Ion Beam, and Theoretical Study.
Deamidation of Protonated Asparagine-Valine Investigated by a Combined Spectroscopic, Guided Ion Beam, and Theoretical Study.
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DOI：
10.1021/acs.jpca.7b12348
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发表时间：
2018-03-08
期刊：
影响因子：
--
通讯作者：
Oomens J
中科院分区：
文献类型：
--
作者：
Kempkes LJM;Boles GC;Martens J;Berden G;Armentrout PB;Oomens J
天冬酰胺残基的肽脱酰胺是一种自发的翻译后修饰，据信其在衰老和若干疾病中起作用。它也是质子化肽的MS/MS谱中众所周知的小分子损失通道。在这里，我们调查的脱酰胺反应，以及其他分解途径，质子化二肽天冬酰胺-缬氨酸（[AsnVal + H]+）后，在低能量激活的质谱仪。使用红外离子光谱，引导离子束串联质谱和理论计算的组合，我们已经能够识别产品离子结构，并确定分解的能量和机制。脱酰胺通过天冬酰胺侧链的氨损失进行，由Asn侧链的γ-碳上的肽键氧的亲核攻击引发。这导致形成含呋喃酮环的产物离子，其特征在于阈值能量为129 ± 5 kJ/mol（能量比[AsnVal + H]+的脱水高15 kJ/mol，[AsnVal + H]+是系统可用的最低能量解离通道）。此处未观察到竞争形成含琥珀酰亚胺环的产物，如已观察到的质子化天冬酰胺-甘氨酸（[AsnGly + H]+）和天冬酰胺-丙氨酸（[AsnAla + H]+）。反应途径的量子化学模型证实了解离行为的这些细微差异。测得的反应阈值与预测的理论反应能量计算在几个层次的理论。
Peptide deamidation of asparaginyl residues is a spontaneous post-translational modification that is believed to play a role in aging and several diseases. It is also a well-known small-molecule loss channel in the MS/MS spectra of protonated peptides. Here we investigate the deamidation reaction, as well as other decomposition pathways, of the protonated dipeptide asparagine–valine ([AsnVal + H]+) upon low-energy activation in a mass spectrometer. Using a combination of infrared ion spectroscopy, guided ion beam tandem mass spectrometry, and theoretical calculations, we have been able to identify product ion structures and determine the energetics and mechanisms for decomposition. Deamidation proceeds via ammonia loss from the asparagine side chain, initiated by a nucleophilic attack of the peptide bond oxygen on the γ-carbon of the Asn side chain. This leads to the formation of a furanone ring containing product ion characterized by a threshold energy of 129 ± 5 kJ/mol (15 kJ/mol higher in energy than dehydration of [AsnVal + H]+, the lowest energy dissociation channel available to the system). Competing formation of a succinimide ring containing product, as has been observed for protonated asparagine–glycine ([AsnGly + H]+) and asparagine–alanine ([AsnAla + H]+), was not observed here. Quantum-chemical modeling of the reaction pathways confirms these subtle differences in dissociation behavior. Measured reaction thresholds are in agreement with predicted theoretical reaction energies computed at several levels of theory.
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DOI：
10.1016/j.jasms.2010.04.017
发表时间：
2010-08-01
影响因子：
3.2
作者：
Boyd, Robert;Somogyi, Arpad
通讯作者：
Somogyi, Arpad
影响因子：
3.3
作者：
Boles, Georgia C.;Wu, R. R.;Armentrout, P. B.
通讯作者：
Armentrout, P. B.
影响因子：
2.3
作者：
Harrison, AG
通讯作者：
Harrison, AG
DOI：
10.1016/s1044-0305(02)00347-1
发表时间：
2002-05-01
影响因子：
3.2
作者：
Armentrout, PB
通讯作者：
Armentrout, PB
影响因子：
15
作者：
Dunkelberger, Emily B.;Buchanan, Lauren E.;Marek, Peter;Cao, Ping;Raleigh, Daniel P.;Zanni, Martin T.
通讯作者：
Zanni, Martin T.