Modelling of the gas-phase phosphate group loss and rearrangement in phosphorylated peptides.
Modelling of the gas-phase phosphate group loss and rearrangement in phosphorylated peptides.
复制标题
磷酸化肽中气相磷酸基团丢失和重排的建模。
DOI：
--
复制
发表时间：
2011
影响因子：
2.3
通讯作者：
M. Rožman
中科院分区：
文献类型：
--
作者：
M. Rožman
用量子力学和莱斯-拉姆斯佩格-卡塞尔-马库斯理论相结合的方法对磷酸化多肽的气相解离进行了模拟。估算了几种低能裂解和重排途径的势能面和单分子反应速率，并提出了一般机理。磷酸的中性损失主要是分子内亲核取代机理的结果。其机理涉及磷酸化氨基酸N-末端羰基氧对β-碳的亲核攻击，生成环状五元恶唑啉产物离子。不管质子的迁移率如何，这条路径要么由可移动的质子引导，要么由一些碱性残基的带正电的侧链引导。虽然磷酸盐流失的机理方面不受质子迁移环境的影响，但它确实影响离子丰度。结果表明，在流动质子环境下，磷酸中性损失产物离子与骨架裂解片段之间应发生相互作用。另一方面，当质子迁移率有限时，中性损失产物离子可能占主导地位。含磷丝氨酸与含磷苏氨酸多肽的裂解动力学表明，含磷苏氨酸多肽的H(3)PO(4)中性损失比含磷丝氨酸类似物少。在离子陷阱仪器中，在毫秒级的低能量CID期间，可能会发生磷酸基团重排，导致磷酸化残基和羟基化残基之间的互换。单分子解离速率常数意味着这种杂乱产物离子的丰度很低。
The gas-phase dissociation of phosphorylated peptides was modelled using a combination of quantum mechanics and the Rice-Ramsperger-Kassel-Marcus theory. Potential energy surfaces and unimolecular reaction rates for several low-energy fragmentation and rearrangement pathways were estimated, and a general mechanism was proposed. The neutral loss of the phosphoric acid was mainly an outcome of the intramolecular nucleophilic substitution mechanism. The mechanism involves a nucleophilic attack of the phosphorylated amino acid N-terminal carbonyl oxygen on β-carbon, yielding a cyclic five-membered oxazoline product ion. Regardless of the proton mobility, the pathway was charge directed either by a mobile proton or by a positively charged side chain of some basic residue. Although the mechanistic aspects of the phosphate loss are not influenced by the proton mobility environment, it does affect ion abundances. Results suggest that under the mobile proton environment, the interplay between phosphoric acid neutral loss product ion and backbone cleavage fragments should occur. On the other hand, when proton mobility is limited, neutral loss product ion may predominate. The fragmentation dynamics of phosphoserine versus phosphothreonine containing peptides suggests that H(3)PO(4) neutral loss from phosphothreonine containing peptides is less abundant than that from their phosphoserine containing analogs. During the low-energy CID of phosphorylated peptides in the millisecond time range, typical for ion trap instruments, a phosphate group rearrangement may happen, resulting in an interchange between the phosphorylated and the hydroxylated residues. Unimolecular dissociation rate constants imply the low abundance of such scrambled product ions.
影响因子：
4.4
作者：
Aguiar M;Haas W;Beausoleil SA;Rush J;Gygi SP
通讯作者：
Gygi SP