EFFECT OF PROLINE RESIDUES ON PROTEIN FOLDING
EFFECT OF PROLINE RESIDUES ON PROTEIN FOLDING
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DOI：
10.1016/0022-2836(81)90342-9
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发表时间：
1981-01-01
影响因子：
5.6
通讯作者：
LEVITT, M
中科院分区：
文献类型：
--
作者：
LEVITT, M
构象能计算已用于研究脯氨酸残基在牛胰蛋白酶抑制剂折叠中的作用。在计算中，这个小蛋白质的 4 个脯氨酸残基中的每一个都被迫从反式肽异构体变成顺式肽异构体，同时仍然是天然折叠结构的一部分。顺式脯氨酸残基总是可以通过天然构象的微小变化来适应（<1.ANG.均方根偏差）。对于 4 个脯氨酸残基中的 3 个（Pro2、Pro9 和 Pro13），计算得出顺式形式会使折叠构象不稳定 < 11 kcal/mol，这表明任一异构体形式都可以快速折叠成稳定的类天然构象。对于这 3 个中的 1 个（Pro13），去稳定性仅为 1 kcal/mol，表明存在 Pro13 顺式的替代折叠天然构象。据计算，第四个脯氨酸残基 Pro8 会破坏天然构象的稳定性（33 kcal/mol），从而以先前提出的方式阻止折叠。
Conformational energy calculations have been used to study the role of the proline residues in the folding of bovine pancreatic trypsin inhibitor. In the calculation, each of the 4 proline residues of this small protein is forced from the trans to cis peptide isomer while still part of the native folded structure. The cis proline residue can always be accommodated by small changes of the native conformation (< 1 .ANG. root-mean-square deviation). For 3 of the 4 proline residues, Pro2, Pro9 and Pro13, being in the cis form is calculated to destabilize the folded conformation by < 11 kcal/mol, suggesting that rapid folding to a stable native-like conformation can occur with either isomeric form. For 1 of these 3, Pro13, the destabilization is only 1 kcal/mol, suggesting the existence of an alternative folded native conformation with Pro13 cis. The 4th proline residue, Pro8, is calculated to destabilize the native conformation by so much (33 kcal/mol) that it will block folding in the manner proposed previously.