Species differences of serum albumins : III. Analysis of structural characteristics and ligand binding properties during N-B transitions

• Published in: Pharmaceutical research Vol. 15; no. 4; pp. 592 - 598
• Main Authors: KOSA, T, MARUYAMA, T, SAKAI, N, YONEMURA, N, YAHARA, S, OTAGIRI, M
• Format: Journal Article
• Language: English
• Published: New York, NY Springer 01.04.1998
• Subjects: Analysis; Animals; Binding Sites; Biological and medical sciences; Cattle; Diazepam - metabolism; Dogs; General pharmacology; Histidine - chemistry; Humans; Hydrogen-Ion Concentration; Ibuprofen - metabolism; Ligands; Medical sciences; Pharmacology. Drug treatments; Phenylbutazone - metabolism; Protein Conformation; Rabbits; Rats; Serum Albumin - chemistry; Serum Albumin - metabolism; Serum Albumin, Bovine - chemistry; Serum Albumin, Bovine - metabolism; Species Specificity; Warfarin - metabolism; Ligand; Psychotropic; Coumarine derivatives; Fluorescence; Anticoagulant; NMR spectrometry; Antivitamin K; Binding capacity; Ibuprofen; Pyrazole derivatives; pH; Benzodiazepine derivatives; Diazepam; Differential scanning calorimetry; Warfarin; Stability; Phenylbutazone; Serum albumin; Circular dichroism; Non steroidal antiinflammatory agent; Chemical modification; Analgesic; Arylacetic acid derivatives; Antipyretic; Conformational transition
• ISSN: 0724-8741; 1573-904X
• DOI: 10.1023/a:1011986028529

The aim of this study was to investigate the characteristics of the structural transitions and changes in ligand binding properties of different albumins during the pH-dependent structural transition, often referred to as the N-B transition. Structural transitions were evaluated by means of spectrometry, differential scanning calorimetry and chemical modification. In addition, ligand binding properties were investigated using typical site-specific bound drugs (warfarin, phenylbutazone, ibuprofen and diazepam). Conformational changes, including N-B transition, clearly occurred in albumins from all species used in this study. The conformational stabilities of all the albumins were clearly lost in the weakly alkaline pH range. This was probably the result of the destruction of salt bridges between domain I and domain III in the albumin molecule. In addition, the profiles of the ANS-induced fluorescence were different and could be classified into two patterns, suggesting that hydrophobic pockets in the albumin molecules were different for the different species. The data suggest that the amino acid residues responsible for the transitions were some of the His residues located in domain I. Further, the ligand binding properties of the albumins were slightly different but statistically significant. The overall mechanisms of the N-B transition may be similar for all the albumins, but its impact is considerably different among the species in terms of both structural characteristics and ligand binding properties. Furthermore, the transitions appear to be multi-step transitions.