Pandey Anil K, Thomas Krista M, Forbes Christina R, Zondlo Neal J
Department of Chemistry and Biochemistry, University of Delaware , Newark, Delaware 19716, United States.
Biochemistry. 2014 Aug 19;53(32):5307-14. doi: 10.1021/bi500696k. Epub 2014 Aug 8.
Aromatic rings exhibit defined interactions via the unique aromatic π face. Aromatic amino acids interact favorably with proline residues via both the hydrophobic effect and aromatic-proline interactions, C-H/π interactions between the aromatic π face and proline ring C-H bonds. The canonical aromatic amino acids Trp, Tyr, and Phe strongly disfavor a polyproline helix (PPII) when they are present in proline-rich sequences because of the large populations of cis amide bonds induced by favorable aromatic-proline interactions (aromatic-cis-proline and proline-cis-proline-aromatic interactions). We demonstrate the ability to tune polyproline helix conformation and cis-trans isomerism in proline-rich sequences using aromatic electronic effects. Electron-rich aromatic residues strongly disfavor polyproline helix and exhibit large populations of cis amide bonds, while electron-poor aromatic residues exhibit small populations of cis amide bonds and favor polyproline helix. 4-Aminophenylalanine is a pH-dependent electronic switch of polyproline helix, with cis amide bonds favored as the electron-donating amine, but trans amide bonds and polyproline helix preferred as the electron-withdrawing ammonium. Peptides with block proline-aromatic PPXPPXPPXPP sequences exhibited electronically switchable pH-dependent structures. Electron-poor aromatic amino acids provide special capabilities to integrate aromatic residues into polyproline helices and to serve as the basis of aromatic electronic switches to change structure.
芳香环通过独特的芳香π面表现出特定的相互作用。芳香族氨基酸通过疏水作用和芳香-脯氨酸相互作用（芳香π面与脯氨酸环C-H键之间的C-H/π相互作用）与脯氨酸残基产生有利的相互作用。当富含脯氨酸的序列中存在典型的芳香族氨基酸色氨酸（Trp）、酪氨酸（Tyr）和苯丙氨酸（Phe）时，由于有利的芳香-脯氨酸相互作用（芳香-顺式脯氨酸和脯氨酸-顺式脯氨酸-芳香相互作用）诱导大量顺式酰胺键的形成，它们强烈不利于多聚脯氨酸螺旋（PPII）。我们证明了利用芳香电子效应来调节富含脯氨酸序列中的多聚脯氨酸螺旋构象和顺反异构的能力。富电子的芳香族残基强烈不利于多聚脯氨酸螺旋，并表现出大量的顺式酰胺键，而贫电子的芳香族残基表现出少量的顺式酰胺键，并有利于多聚脯氨酸螺旋。4-氨基苯丙氨酸是多聚脯氨酸螺旋的pH依赖性电子开关，作为供电子胺时有利于顺式酰胺键，但作为吸电子铵时则更倾向于反式酰胺键和多聚脯氨酸螺旋。具有脯氨酸-芳香族PPXPPXPPXPP序列的肽表现出电子可切换的pH依赖性结构。贫电子的芳香族氨基酸具有特殊的能力，能够将芳香族残基整合到多聚脯氨酸螺旋中，并作为改变结构的芳香电子开关的基础。
