CAJ | 학술논문

多肽和蛋白质中Xaa-Pro片段肽脯酰胺键顺反异构对其构象与功能有重要影响.设计合成了一系列模型多肽及其磷酸化多肽,并采用核磁共振实验和分子动力学模拟的方法,研究了所合成多肽中肽脯酰胺键的顺反异构化.结果表明,对脯氨酸之前的Xaa残基进行侧链O-磷酸化会极大地影响该顺反异构化过程,进而调节肽链构象.此外,磷酸化使得多肽顺式构象比例增加,且当磷酸基团不带负电荷时顺式构象所占比例最大.同时,分子动力学模拟所得结果与核磁共振实验相一致,包括最稳定构象和顺反构象统计分布.磷酸基团所带电荷及其空间位阻可能是影响这类磷酸化多肽构象变化的主要因素.
다태화단백질중Xaa-Pro편단태포선알건순반이구대기구상여공능유중요영향.설계합성료일계렬모형다태급기린산화다태,병채용핵자공진실험화분자동역학모의적방법,연구료소합성다태중태포선알건적순반이구화.결과표명,대포안산지전적Xaa잔기진행측련O-린산화회겁대지영향해순반이구화과정,진이조절태련구상.차외,린산화사득다태순식구상비례증가,차당린산기단불대부전하시순식구상소점비례최대.동시,분자동역학모의소득결과여핵자공진실험상일치,포괄최은정구상화순반구상통계분포.린산기단소대전하급기공간위조가능시영향저류린산화다태구상변화적주요인소.
The peptidyl-prolyl imide bond cis/trans isomerization of Xaa-Pro motif in the peptide and protein plays an important role to influence their conformation and function. Here, a series of model peptides including phosphorylated and its unphosphorylated counterparts were designed and synthesized. Preliminary 1H NMR experiments and molecular dynamics (MD) simulation were used to analyze the peptidyl-prolyl cis/trans imide bond isomerization. The data indicated that the side-chain O-phosphorylation of the Xaa residues preceding proline affected evidently the isomerization and thereby regulated the peptides conformations. The charges of the phosphate moiety as well as their steric effects might be the driving force for the conformational changes of these phosphopeptides.Moreover, the obtained most stable multiple configurations and their statistic cis/trans concentration distribution in MD simulation were basically consistent with the NMR experiments, which demonstrated that phosphorylation increased the cis conformation of the peptide and the maximum cis ratio is given while the phosphate group has no negative charge.