Quantifying the structural requirements of the folding transition state of protein A and other systems.
Quantifying the structural requirements of the folding transition state of protein A and other systems.
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DOI：
10.1016/j.jmb.2008.06.067
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发表时间：
2008-09-19
影响因子：
5.6
通讯作者：
Sosnick, Tobin R.
中科院分区：
文献类型：
--
作者：
Baxa, Michael C.;Freed, Karl F.;Sosnick, Tobin R.
蛋白质A的b结构域（BdpA）是一个小的3螺旋束，一直是大量实验和理论研究的主题。然而，对于过渡态系综（TSE）的结构仍然缺乏统一的认识。为了表征这种令人惊讶的具有挑战性的蛋白质的TSE，我们结合了ψ分析（探测特定侧链接触的作用）和动力学H/D酰胺同位素效应（测量氢键含量），建立在先前使用突变φ分析（探测侧链取代的能量影响）的研究基础上。第二螺旋（H2）在TSE中折叠，而螺旋形成分别出现在第一和第三螺旋的羧基端和氨基端。实验数据表明，具有原生拓扑结构的同质塑料TS。该研究推广了我们先前基于两个较大的α/β蛋白的结论，即大多数小蛋白的tse达到其天然状态相对接触顺序的70%左右。这种高百分比限制了可能的TS异质性程度，需要重新评估其他蛋白质的TSE结构含量，特别是当它们的特征是小或极化时。
The B-domain of protein A (BdpA) is a small 3-helix bundle that has been the subject of considerable experimental and theoretical investigation. Nevertheless, a unified view of the structure of the transition state ensemble (TSE) is still lacking. To characterize the TSE of this surprisingly challenging protein, we apply a combination of ψ-analysis (which probes the role of specific side chain to side chain contacts) and kinetic H/D amide isotope effects (which measures of hydrogen bond content), building upon previous studies using mutational φ-analysis (which probes the energetic influence of side chain substitutions). The second helix (H2) is folded in the TSE, while helix formation appears just at the carboxy and amino termini of the first and third helices, respectively. The experimental data suggest a homogenous, yet plastic TS with a native-like topology. This study generalizes our earlier conclusion, based on two larger α/β proteins, that the TSEs of most small proteins achieve ~70% of their native state’s relative contact order. This high percentage limits the degree of possible TS heterogeneity and requires a re-evaluation of the structural content of the TSE of other proteins, especially when they are characterized as small or polarized.
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DOI：
10.1073/pnas.2335541100
发表时间：
2003-11-25
影响因子：
11.1
作者：
García, AE;Onuchic, JN
通讯作者：
Onuchic, JN
影响因子：
4.4
作者：
Eyring, H
通讯作者：
Eyring, H
影响因子：
8
作者：
Bai, YW;Karimi, A;Wright, PE
通讯作者：
Wright, PE
影响因子：
2.9
作者：
ABKEVICH, VI;GUTIN, AM;SHAKHNOVICH, EI
通讯作者：
SHAKHNOVICH, EI
DOI：
10.1038/1354
发表时间：
1998-08-01
期刊：
NATURE STRUCTURAL BIOLOGY
影响因子：
--
作者：
Gruebele, M;Wolynes, PG
通讯作者：
Wolynes, PG