ELECTRON TRANSFER DISSOCIATION OF A MELECTIN PEPTIDE: CORRELATING THE PRECURSOR ION STRUCTURE WITH PEPTIDE BACKBONE DISSOCIATIONS
ELECTRON TRANSFER DISSOCIATION OF A MELECTIN PEPTIDE: CORRELATING THE PRECURSOR ION STRUCTURE WITH PEPTIDE BACKBONE DISSOCIATIONS
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DOI：
10.1135/cccc2011025
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发表时间：
2011-01-01
影响因子：
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通讯作者：
Turecek, Frantisek
中科院分区：
文献类型：
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作者：
Moss, Christopher L.;Chung, Thomas W.;Turecek, Frantisek
两亲N-末端十肽GFLSILKKVL-NH2片段的双电荷和三电荷离子的电子转移解离(ETD)给出了不同分布的碎片离子。三重带电离子产生了广泛的C和Z型碎片离子系列，覆盖了从N和C末端的整个序列。相反，电子转移到双电荷离子会导致主干断裂，发生在靠近N和C末端的残基上。一个自由的低能电子附着在双电荷离子上，导致靠近N和C端的初级解离，随后是z离子的连续解离。采用力场分子动力学穷尽构象搜索、半经验PM6方法进行大规模梯度优化、密度泛函理论单点能量和梯度优化计算相结合的方法，对多肽中气态双电荷离子的结构进行了研究。最稳定的双电荷离子被发现在赖氨酸e-氨基上质子化，并具有球状构象。ETD中的主干裂解与电子结合到最稳定构象上所产生的阳离子自由基的电子结构有关。带电的赖氨酸氨基将电子引导到Phe、Leu、Lys和Val残基上最接近的酰胺基团上的pi*轨道，这些基团显示出最高的自旋密度。这些酰胺基团上的电子连接削弱了Phe-Leu、Leu-Ser、Lys-Lys和Lys-Val残基之间的N-C-α键，并导致主链解离。
Electron transfer dissociation (ETD) of doubly and triply charged ions from the amphipathic N-terminal decapeptide GFLSILKKVL-NH2 segment of melectin gave different distributions of fragment ions. The triply charged ions generated extensive series of fragment ions of c and z type that covered the entire sequence from both the N and C termini. In contrast, electron transfer to the doubly charged ions caused backbone cleavages that occurred at residues close to the N and C termini. Attachment of a free low-energy electron to the doubly charged ions caused primary dissociations close to the N and C termini that were followed by consecutive dissociations of z ions. The structure of gaseous doubly charged ions from the melectin peptide was elucidated by a combination of exhaustive conformational search by force-field molecular dynamics, large-scale gradient optimization using the semiempirical PM6 method, and density functional theory single-point energy and gradient optimization calculations. The most stable doubly charged ions were found to be protonated at the lysine e-amino groups and have globular conformations. The backbone cleavages in ETD correlated with the electronic structure of cation-radicals produced by electron attachment to the most stable conformers. The charged lysine ammonium groups direct the incoming electron to the pi* orbitals at the proximate amide groups at Phe, Leu, Lys and Val residues that show the highest spin densities. Electron attachment at these amide groups weakens the N-C-alpha bonds between the Phe-Leu, Leu-Ser, Lys-Lys and Lys-Val residues and causes backbone dissociations.