Ligand entry in human ileal bile acid-binding protein is mediated by histidine protonation.

ABSTRACT: Human ileal bile acid-binding protein (hI-BABP) has a key role in the intracellular transport of bile salts. To explore the role of histidine protonation in the binding process, the pH-dependence of bile salt binding and internal dynamics in hI-BABP was investigated using NMR spectroscopy and biophysical tools. Thermodynamic and kinetic measurements show an increase in the overall binding affinity and the association rate constant of the first binding step below the pK_a of the histidines, suggesting that ligand binding is favoured by the protonated state. The overlap between residues exhibiting a high sensitivity to pH in their backbone amide chemical shifts and protein regions undergoing a global ms conformational exchange indicate a connection between the two processes. Accord

SUBMITTER: Horvath G 

PROVIDER: S-EPMC6423008 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature