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On the interaction of polypeptides with bile salts or bilirubin‐IXα
Author(s) -
D'Alagni Maria,
D'Archivio Angelo A.,
Giglio Edoardo
Publication year - 1993
Publication title -
biopolymers
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.556
H-Index - 125
eISSN - 1097-0282
pISSN - 0006-3525
DOI - 10.1002/bip.360331006
Subject(s) - chemistry , salt (chemistry) , enantiomer , bile acid , hydrogen bond , aqueous solution , amino acid , hydrophobic effect , stereochemistry , crystallography , molecule , biochemistry , organic chemistry
Aqueous solutions formed by polypeptides, simple models of proteins, and bile salts (sodium cholate and deoxycholate, NaC and NaDC, respectively) or bilirubin‐IXα (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 α‐helical conformation. The α‐helix content increases with increasing bile salt concentration and ionic strength. NaDC seems to be a slightly better stabilizing agent of the α‐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 α‐helices toward the left‐ and right‐handed enantiomer of BR, respectively. BR is bound to ‐NH 2 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. © 1993 John Wiley & Sons, Inc.