Effect of the N2 residue on the stability of the α-helix for all 20 amino acids
Effect of the N2 residue on the stability of the α-helix for all 20 amino acids
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DOI：
10.1110/ps.50701
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发表时间：
2001-07-01
期刊：
影响因子：
8
通讯作者：
Doig, AJ
中科院分区：
文献类型：
--
作者：
Cochran, DAE;Doig, AJ
N2是cr-螺旋中的第二个位置。所有20个氨基酸都被放置在一个合成的螺旋肽(CH3CO-[AXAAAKAAAAAAAAAAAAAAAAAGY]-NH2)的N_2位，并在273K用圆二色光谱测定螺旋含量。用修正的Lifson-Roig螺旋线圈理论分析了多肽螺旋度对N_2残基同一性的依赖关系，该理论包括N_2能量参数(N_2)。Delta DeltaG((相对于Ala))的等级顺序是Glu(-)，Asp(-)&Gt；Ala&Gt；Glu(0)，Leu，Val，Gin，Thr，Lie，Ser，Met，Asp(0)，His(0)，Arg，Cys，Lys，Phe&Gt；Asn，>；Gly，His(+)，Pro，Tyr。结果与蛋白质中的N_2倾向有很好的相关性，与N1和螺旋内部偏好有一定程度的相关性，而与N-帽偏好无关。最强的能量效应来自与螺旋偶极的相互作用，螺旋偶极有利于螺旋N端的负电荷。与N-帽位置相反，在氮的侧链上，如Gin、Ser和Thr的氢键很弱，尽管在蛋白质晶体结构中经常发生。这是因为N-帽氢键接近线性，而氮氢键的几何构型较差。这些结果可用于合理修改蛋白质的稳定性，帮助设计螺旋，并改进螺旋位置和稳定性的预测。
N2 is the second position in the cr-helix. All 20 amino acids were placed in the N2 position of a synthetic helical peptide (CH3CO-[AXAAAAKAAAAKAAGY]-NH2) and the helix content was measured by circular dichroism spectroscopy at 273K. The dependence of peptide helicity on N2 residue identity has been used to determine a free-energy scale by analysis with a modified Lifson-Roig helix-coil theory that includes a parameter for the N2 energy (n2). The rank order of Delta DeltaG((relative to Ala)) is Glu(-), Asp(-) > Ala > Glu(0), Leu, Val, Gin, Thr, lie, Ser, Met, Asp(0), His(0), Arg, Cys, Lys, Phe > Asn, > Gly, His(+), Pro, Tyr. The results correlate very well with N2 propensities in proteins, moderately well with N1 and helix interior preferences, and not at all with N-cap preferences. The strongest energetic effects result from interactions with the helix dipole, which favors negative charges at the helix N terminus. Hydrogen bonds to side chains at N2, such as Gin, Ser, and Thr, are weak, despite occurring frequently in protein crystal structures, in contrast to the N-cap position. This is because N-cap hydrogen bonds are close to linear, whereas N2 hydrogen bonds have poor geometry. These results can be used to modify protein stability rationally, help design helices, and improve prediction of helix location and stability.