Effect of prototypic drugs ibuprofen and warfarin on global chaotropic unfolding of human serum heme-albumin: a fast-field-cycling 1H-NMR relaxometric study.
Human serum albumin (HSA) is the most prominent protein in plasma, but it is also found in tissues and secretions throughout the body. The three-domain design of HSA provides a variety of binding sites for many ligands, including heme and drugs. HSA has been used as a model multidomain protein to investigate how interdomain interactions affect the global folding/unfolding process. Here, we report on the reversible chemical denaturation of heme-HSA involving three different conformational states (F, N, and B, occurring at pH 4.0, 7.0, and 9.0, respectively) and on the effect of prototypic drugs ibuprofen and warfarin on thermodynamics of the reversible unfolding process. Chaotropic unfolding of heme-HSA in the F, N, and B conformations is governed by different thermodynamic regimes, with the B form showing an entropic stabilization of the structure that compensates an enthalpic destabilization, and the F form easily unfolding under entropic control. Warfarin and ibuprofen binding stabilizes heme-HSA in both N and B states.
Fanali
Gabriella
G
Dipartimento di Biologia Strutturale e Funzionale, and Centro di Neuroscienze, Università dell'Insubria, Via Alberto da Giussano 12, I-21052 Busto Arsizio (VA), Italy.
Ascenzi
Paolo
P
Fasano
Mauro
M
D006801:Humans; D007052:Ibuprofen / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy / Q000295:instrumentation / Q000379:methods*; D008705:Methemalbumin / Q000737:chemistry* / Q000187:drug effects; D011487:Protein Conformation; D011489:Protein Denaturation / Q000187:drug effects*; D017510:Protein Folding; D013816:Thermodynamics; D014859:Warfarin / Q000494:pharmacology*
D008705:Methemalbumin; D014859:Warfarin; D007052:Ibuprofen