A disulfide bridge allows for site-selective binding in liver bile acid binding protein thereby stabilising the orientation of key amino acid side chains

Chemistry. 2012 Mar 5;18(10):2857-66. doi: 10.1002/chem.201102203. Epub 2012 Feb 1.


The presence of a disulfide bridge in liver bile acid binding protein (L-BABP/S-S) allows for site-selective binding of two bile acids, glycochenodeoxycholic (GCDA) and glycocholic acid (GCA), differing only in the presence of a hydroxyl group. The protein form devoid of the disulfide bridge (L-BABP) binds both bile salts without discriminating ability. We investigate the determinants of the molecular recognition process in the formation of the heterotypic L-BABP/S-S complex with GCDA [corrected] and GCA [corrected] located in the superficial and inner protein sites, respectively. The comparison of the NMR spectroscopy structure of heterotypic holo L-BABP/S-S, the first reported for this protein family, with that of the homotypic L-BABP complex demonstrates that the introduction of a S-S link between adjacent strands changes the conformation of three key residues, which function as hot-spot mediators of molecular discrimination. The favoured χ(1) rotameric states (t, g(+) and g(-) for E99, Q100 and E109 residues, respectively) allow the onset of an extended intramolecular hydrogen-bond network and the consequent stabilisation of the side-chain orientation of a buried histidine, which is capable of anchoring a specific ligand.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acids / chemistry*
  • Binding Sites
  • Carrier Proteins / chemistry*
  • Carrier Proteins / metabolism
  • Disulfides / chemistry*
  • Humans
  • Liver / chemistry*
  • Membrane Glycoproteins / chemistry*
  • Membrane Glycoproteins / metabolism
  • Models, Molecular
  • Nuclear Magnetic Resonance, Biomolecular


  • Amino Acids
  • Carrier Proteins
  • Disulfides
  • Membrane Glycoproteins
  • bile acid binding proteins