Inductive effects on the structure of proline residues.
Inductive effects on the structure of proline residues.
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DOI：
10.1111/j.1399-3011.1994.tb00169.x
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发表时间：
2009-01
期刊：
影响因子：
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通讯作者：
Nicholas Panasik;E. Eberhardt;Arthur S. Edison;Douglas R. Powell;Ronald T. Raines
中科院分区：
文献类型：
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作者：
Nicholas Panasik;E. Eberhardt;Arthur S. Edison;Douglas R. Powell;Ronald T. Raines
4(S)-羟脯氨酸（Hyp）残基约占大多数胶原蛋白的10%，胶原蛋白是脊椎动物中含量最多的蛋白质。用x射线衍射分析确定了脯氨酸残基羟基诱导效应对脯氨酸残基结构的影响。合成了n -乙酰脯氨酸甲基lester(1)、n -乙酰-4(S)-羟脯氨酸甲基lester(2)和n -乙酰-4(S)-氟脯氨酸甲基lester(3)，并对它们的晶体结构进行了高分辨率测定。晶体1的酰胺键呈顺式构象，是溶液中的次要异构体，1的吡咯烷环具有C - γ -内凹。在结晶2和结晶3中，酰胺键呈反式构象，吡咯烷环呈c -外显子折叠。在RHF/3- 21g水平上，用从头算分子轨道计算得到了吡咯烷环中sp3杂化碳原子间键的长度明显短于1和2。其他1、2、3键的键长未见明显变化。氮原子的金字塔化程度以1 < 2 < 3的顺序显著增加。综上所述，这些结果表明脯氨酸残基4位的吸电子取代基对这些残基的结构有显著的影响。特别是，金字塔化的变化表明，这些取代基增加了脯氨酸氮原子的sp3特征，从而改变了脯氨酸肽键异构化的速率。
4(S)-Hydroxyproline (Hyp) residues constitute about 10% of most forms of collagen, the most abundant protein in vertebrates. X-Ray diffraction analysis was used to ascertain how the structure of proline residues is affected by the inductive effect elicited by the hydroxyl group of Hyp residues. N-Acetylproline methylester (1), N-acetyl-4(S)-hydroxyproline methylester (2) and N-acetyl-4(S)- fluoroproline methylester (3) were synthesized, and their crystalline structures were determined at high resolution. The amide bond of crystalline 1 was in the cis conformation, which is the minor isomer in solution, and the pyrrolidine ring of 1 had C gamma-endo pucker. In crystalline 2 and 3 the amide bonds were in the trans conformation, and the pyrrolidine rings had C-exo pucker. The lengths of the bonds between sp3-hybridized carbon atoms in the pyrrolidine ring were significantly shorter in 2 and 3 than in 1, as was predicted by ab initio molecular orbital calculations at the RHF/3-21G level of theory. No significant change in bond length was observed in the other bonds of 1,2 or 3. The pyramidylization of the nitrogen atom increased dramatically in the order: 1 < 2 < 3. Together, these results indicate that electron-withdrawing substituents in the 4-position of proline residues can have a significant influence on the structure of these residues. In particular, the change in pyramidylization suggests that such substituents increase the sp3-character of the prolyl nitrogen atom and could thereby alter the rate of prolyl peptide bond isomerization.