Modulation of intrinsic phi,psi propensities of amino acids by neighbouring residues in the coil regions of protein structures: NMR analysis and dissection of a beta-hairpin peptide.
Modulation of intrinsic phi,psi propensities of amino acids by neighbouring residues in the coil regions of protein structures: NMR analysis and dissection of a beta-hairpin peptide.
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蛋白质结构线圈区域中相邻残基对氨基酸内在 phi,psi 倾向的调节：NMR 分析和 β-发夹肽的解剖。
DOI：
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发表时间：
1998
影响因子：
5.6
通讯作者：
M. Searle
中科院分区：
文献类型：
--
作者：
S. Griffiths;G. Sharman;A. J. Maynard;M. Searle
蛋白质结构卷曲区残基的分析提供了一种新的方法去卷积各种竞争因子，这些竞争因子决定了氨基酸的内在phi，psi倾向，而不受与β-链和α-螺旋相关的常规相互作用的影响。我们已经考虑了上下文对phi，psi偏好的作用，通过检查相邻残基在512个高分辨率，低同源性结构的数据库内调制线圈倾向的影响。在一般情况下，当侧翼残基是β-支链或芳香族（瓦尔、Ile、Tyr和Phe）时，β-倾向（P β）显著增加，这主要是由于侧翼残基之间的空间效应。更微妙的残基特异性的影响是显而易见的，当P β值进行详细检查，显示“随机卷曲”构象是高度序列依赖性的。侧翼残基对phi分布的影响已被用于计算上下文相关的平均3 JNH-Ha偶联常数。我们在模型16个残基的β-发夹肽、“突变”发夹（VSI-->KSK序列变化）和两个发夹的分离的C末端β链片段的折叠背景下检查了这些发现。我们发现一个更好的3 JNH-Halpha值之间的相关性来自数据库模型和实验确定的上下文相关的phi分布时，被认为是。两个发夹的单个C末端β链序列（GKKITVSI与GKKITKSK）在不同程度上倾向于形成延伸的β样构象。在这种情况下，构象“倾向”可能对β-发夹稳定性有显著贡献。
Analysis of residues in coil regions of protein structures presents a novel approach to deconvoluting the various competing factors which determine the intrinsic phi,psi propensities of amino acids free from the regular interactions associated with beta-strands and alpha-helices. We have considered the role of context on phi,psi preferences by examining the effects of neighbouring residues in modulating coil propensities within a data base of 512 high-resolution, low-homology structures. In the general case, when flanking residues are beta-branched or aromatic (Val, Ile, Tyr and Phe) the beta-propensity (Pbeta) increases significantly, largely due to steric effects between flanking residues. More subtle residue-specific effects are apparant when Pbeta values are examined in detail, showing "random coil" conformations to be highly sequence-dependent. The effects of flanking residues on phi distributions have been used to calculate context-dependent average 3JNH-Halpha coupling constants. We have examined these findings in the context of the folding of a model 16-residue beta-hairpin peptide, "mutant" hairpin (VSI-->KSK sequence change) and the isolated C-terminal beta-strand fragments of both hairpins. We find a better correlation between 3JNH-Halpha values derived from the data base model and those determined experimentally when context-dependent phi distributions are considered. The individual C-terminal beta-strand sequences (GKKITVSI versus GKKITKSK) of the two hairpins are predisposed to different extents to formation of an extended beta-like conformation. Conformational "predisposition" in this context may contribute significantly to beta-hairpin stability.
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DOI：
10.1073/pnas.83.21.8069
发表时间：
1986-11-01
影响因子：
11.1
作者：
BALDWIN, RL
通讯作者：
BALDWIN, RL
影响因子：
5.6
作者：
DYSON, HJ;MERUTKA, G;WRIGHT, PE
通讯作者：
WRIGHT, PE
固体模型化合物和蛋白质展开的热力学。
影响因子：
5.6
作者：
Murphy,KP;Gill,SJ
通讯作者：
Gill,SJ
变性牛胰腺胰蛋白酶抑制剂中疏水簇的形成。
影响因子：
5.6
作者：
Lumb,KJ;Kim,PS
通讯作者：
Kim,PS