Peptide Secondary Structures in the Gas Phase: Consensus Motif of N-Linked Glycoproteins
Peptide Secondary Structures in the Gas Phase: Consensus Motif of N-Linked Glycoproteins
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DOI：
10.1021/ja808687j
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发表时间：
2009-01-28
影响因子：
15
通讯作者：
Simons, John P.
中科院分区：
文献类型：
--
作者：
Cocinero, Emilio J.;Stanca-Kaposta, E. Cristina;Simons, John P.
通过在气相中使用红外激光离子浸光谱结合从头计算和密度泛函理论计算，确定加帽寡肽 Ac-NGS-NHBn 和两个“突变体”Ac-QGS-NHBn 和 Ac-NPS-NHBn 的内在二级结构，解决了二级结构作为自然选择所有 N 连接糖蛋白中共有序列子 NXS/T 的主要决定因素的可能性。它们的全局最小能量构象专门或优先分布在所有三种肽中，显示出显着差异。 NGS采用开放的S形主干构象，而不是之前所有测量都在解决方案中确定的C-10“Asx”转角结构；这种差异可能与“Asx”构象的高偶极矩和极地环境中的结构选择有关。 QGS 采用类似但更刚性的主链结构，由明显更强的氢键支撑。 NPS 采用 Asx 转角与 C-10 U 形转角骨架构象耦合，这种结构也在晶体环境中采用。这些和其他更微妙的结构差异，特别是那些涉及与甲酰胺侧链相互作用的差异，为结构限制的运作提供了强有力的证据，并为天冬酰胺侧链对酶促糖基化的独特反应性提供了潜在的见解。
The possibility of secondary structure acting as a primary determinant in nature's choice of the consensus sequon, NXS/T in all N-linked glycoproteins, has been addressed by determining the intrinsic secondary structures of the capped oligopeptide, Ac-NGS-NHBn, and two "mutants", Ac-QGS-NHBn and Ac-NPS-NHBn, by use of infrared laser ion dip spectroscopy in the gas phase coupled with ab initio and density functional theory calculation. Their global minimum energy conformations, exclusively or preferentially populated in all three peptides, display marked differences. NGS adopts an open, S-shaped backbone conformation rather than the C-10 "Asx" turn structure that all previous measurements have identified in solution; the difference can be related to the high dipole moment of the "Asx" conformation and structural selection in a polar environment. QGS adopts a similar but more rigid backbone structure, supported by markedly stronger hydrogen bonds. NPS adopts an Asx turn coupled with a C-10 U-turn backbone conformation, a structure also adopted in a crystal environment. These and other more subtle structural differences, particularly those involving interactions with the carboxamide side chain, provide strong evidence for the operation of structural constraints, and a potential insight into the unique reactivity of the asparagine side chain toward enzymatic glycosylation.