β-Sheet folding mechanisms from perturbation energetics
β-Sheet folding mechanisms from perturbation energetics
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DOI：
10.1016/j.sbi.2006.01.014
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发表时间：
2006-02-01
影响因子：
6.8
通讯作者：
Kelly, JW
中科院分区：
文献类型：
--
作者：
Deechongkit, S;Nguyen, H;Kelly, JW
酰胺主链和侧链诱变数据可以与动力学和热力学测量相结合，以了解主链氢键和疏水效应对获得β -片结构的能量贡献。例如，已经发现WW结构域的环路1在过渡状态下形成，这与新出现的主题一致，即反向形成是β -片折叠的速率限制。WW结构域残基的一个独特子集主要通过形成氢键和疏水相互作用来稳定天然状态，从而影响热力学稳定性。高能数据和序列挖掘表明，只需要序列中包含的一小部分分子信息或在高分辨率结构中观察到的分子信息就可以生成折叠的功能β -片，这与进化稳健性相一致。
Amide backbone and sidechain mutagenesis data can be used in combination with kinetic and thermodynamic measurements to understand the energetic contributions of backbone hydrogen bonding and the hydrophobic effect to the acquisition of beta-sheet structure. For example, it has been revealed that loop 1 of the WW domain forms in the transition state, consistent with the emerging theme that reverse turn formation is rate limiting in beta-sheet folding. A distinct subset of WW domain residues principally influences thermodynamic stability by forming hydrogen bonds and hydrophobic interactions that stabilize the native state. Energetic data and sequence mining reveal that only a small subset of the molecular information contained in sequences or observed in high-resolution structures is required to generate folded functional beta-sheets, consistent with evolutionary robustness.