On the structure of albumin-bound bilirubin. Selective binding of intramolecularly hydrogen-bonded conformational enantiomers.
The intramolecularly hydrogen-bonded bichromophoric tetrapyrrole pigments, bilirubin-IX alpha and mesobilirubin-XIII alpha, adopt either of two folded, intramolecularly hydrogen-bonded, enantiomeric conformations which are in dynamic equilibrium in solution. Added human serum albumin binds preferentially, although not necessarily exclusively, to one conformational enantiomer, and the solutions exhibit bisignate circular dichroism Cotton effects in the region of the pigment's long wavelength electronic transition. In contrast, the bichromophoric tetrapyrrole pigment mesobilirubin-IV alpha, which is incapable of adopting intramolecularly hydrogen-bonded folded conformations, and the monochromophoric pyrromethenone, xanthobilirubic acid, show only monosignate induced circular dichroism Cotton effects under the same conditions. Application of exciton coupling theory indicates a preference for complexation of the right-handed (or positive) chirality conformational enantiomer of bilirubin-IX alpha or mesobilirubin-XIII alpha to human serum albumin at physiologic pH.
Lightner
D A
DA
Reisinger
M
M
Landen
G L
GL
D001663:Bilirubin / Q000378:metabolism*; D002942:Circular Dichroism; D006801:Humans; D006860:Hydrogen Bonding; D007536:Isomerism; D011485:Protein Binding; D011487:Protein Conformation; D012709:Serum Albumin / Q000378:metabolism*; D013056:Spectrophotometry, Ultraviolet
D012709:Serum Albumin; D001663:Bilirubin