D'Alagni M, D'Archivio A A, Giglio E
Dipartimento di Chimica, Università di Roma La Sapienza, Italy.
Biopolymers. 1993 Oct;33(10):1553-65. doi: 10.1002/bip.360331006.
Aqueous solutions formed by polypeptides, simple models of proteins, and bile salts (sodium cholate and deoxycholate, NaC and NaDC, respectively) or bilirubin-IX alpha (BR) have been studied by CD measurements. They could mimic more complicated biliary systems, thus supplying a possible interpretation of the behavior of some amino acid residues in the biliary proteins. The aggregation of NaDC and NaC in water can be monitored by CD measurements. Bile salts, in submicellar and micellar form, stabilize poly(L-Lys) (PLL) in alpha-helical conformation. The alpha-helix content increases with increasing bile salt concentration and ionic strength. NaDC seems to be a slightly better stabilizing agent of the alpha-helix conformation than NaC. Models characterized by hydrogen bonds between bile salts and PLL are proposed, also resorting to previous data available on the systems formed by NaDC and poly(L-Leu-L-Leu-L-Lys) (PLLL) or poly(L-Leu-L-Leu-L-Asp) (PLLA). Binding of BR to PLL, poly(D-Lys), poly(L-Glu), PLLL, and PLLA in water has been investigated by CD spectra in order to clarify the nature of the association complexes and the mechanism of the BR enantioselective complexation. Potential energy calculations provide binding models capable of explaining the enantioselective ability of the PLL and PLLL alpha-helices toward the left- and right-handed enantiomer of BR, respectively. BR is bound to -NH2 groups of PLL and PLLL lying on a right- and left-handed spiral, respectively. These results, together with those formerly obtained for some bile salts-BR systems, indicate that the selectivity originates from a binding that involves large regions of the BR molecule and gives rise, very probably, to moderate conformational changes from the "ridge tile" structure observed in the crystals. In some cases van der Waals forces can play a crucial role in the chiral recognition of bilirubin. Moreover, possible interaction models of BR with human serum albumin are proposed on the basis of a recent x-ray crystal structure of the protein.
通过圆二色性（CD）测量研究了由多肽、蛋白质的简单模型以及胆汁盐（分别为胆酸钠和脱氧胆酸钠，即NaC和NaDC）或胆红素-IXα（BR）形成的水溶液。它们可以模拟更复杂的胆汁系统，从而为胆汁蛋白中某些氨基酸残基的行为提供一种可能的解释。通过CD测量可以监测NaDC和NaC在水中的聚集情况。亚胶束和胶束形式的胆汁盐能稳定处于α-螺旋构象的聚（L-赖氨酸）（PLL）。α-螺旋含量随胆汁盐浓度和离子强度的增加而增加。NaDC似乎比NaC对α-螺旋构象的稳定作用稍好。提出了以胆汁盐与PLL之间的氢键为特征的模型，同时也参考了之前关于由NaDC和聚（L-亮氨酸-L-亮氨酸-L-赖氨酸）（PLLL）或聚（L-亮氨酸-L-亮氨酸-L-天冬氨酸）（PLLA）形成的体系的现有数据。通过CD光谱研究了BR在水中与PLL、聚（D-赖氨酸）、聚（L-谷氨酸）、PLLL和PLLA的结合，以阐明缔合复合物的性质以及BR对映选择性络合的机制。势能计算提供了能够分别解释PLL和PLLLα-螺旋对BR左旋和右旋对映体的对映选择性能力的结合模型。BR分别与位于右手螺旋和左手螺旋上的PLL和PLLL的-NH2基团结合。这些结果与之前在一些胆汁盐-BR体系中获得的结果一起表明，选择性源于涉及BR分子大片区域的结合，很可能导致从晶体中观察到的“屋脊瓦”结构发生适度的构象变化。在某些情况下，范德华力在胆红素的手性识别中可能起关键作用。此外，基于该蛋白质最近的X射线晶体结构，提出了BR与人血清白蛋白可能的相互作用模型。
