Effect of prototypic drugs ibuprofen and warfarin on global chaotropic unfolding of human serum heme-albumin: a fast-field-cycling 1H-NMR relaxometric study.


Abstract

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. Study holds ProTherm entries: 23713, 23714, 23715, 23716, 23717, 23718, 23719, 23720, 23721, 23722, 23723, 23724 Extra Details: Human serum heme-albumin; 1H NMR relaxometry; Unfolding; Ibuprofen; Warfarin

Submission Details

ID: zHyreKKU3

Submitter: Connie Wang

Submission Date: April 24, 2018, 8:54 p.m.

Version: 1

Publication Details
Fanali G;Ascenzi P;Fasano M,Biophys. Chem. (2007) Effect of prototypic drugs ibuprofen and warfarin on global chaotropic unfolding of human serum heme-albumin: a fast-field-cycling 1H-NMR relaxometric study. PMID:17531369
Additional Information

Structure view and single mutant data analysis

Study data

No weblogo for data of varying length.
Colors: D E R H K S T N Q A V I L M F Y W C G P
 

Data Distribution

Studies with similar sequences (approximate matches)

Correlation with other assays (exact sequence matches)


Relevant PDB Entries

Structure ID Release Date Resolution Structure Title
1AO6 1997-07-18T00:00:00+0000 2.5 CRYSTAL STRUCTURE OF HUMAN SERUM ALBUMIN
1BJ5 1998-07-02T00:00:00+0000 2.5 HUMAN SERUM ALBUMIN COMPLEXED WITH MYRISTIC ACID
1BKE 1998-07-06T00:00:00+0000 3.15 HUMAN SERUM ALBUMIN IN A COMPLEX WITH MYRISTIC ACID AND TRI-IODOBENZOIC ACID
1BM0 1998-07-28T00:00:00+0000 2.5 CRYSTAL STRUCTURE OF HUMAN SERUM ALBUMIN
1E78 2000-08-25T00:00:00+0000 2.6 Crystal structure of human serum albumin
1E7A 2000-08-26T00:00:00+0000 2.2 Crystal structure of human serum albumin complexed with the general anesthetic propofol
1E7B 2000-08-26T00:00:00+0000 2.38 Crystal structure of human serum albumin complexed with the general anesthetic halothane
1E7C 2000-08-26T00:00:00+0000 2.4 HUMAN SERUM ALBUMIN COMPLEXED WITH MYRISTIC ACID and the general anesthetic halothane
1E7E 2000-08-29T00:00:00+0000 2.5 HUMAN SERUM ALBUMIN COMPLEXED WITH DECANOIC ACID (CAPRIC ACID)
1E7F 2000-08-29T00:00:00+0000 2.43 HUMAN SERUM ALBUMIN COMPLEXED WITH DODECANOIC ACID (LAURIC ACID)

Relevant UniProtKB Entries

Percent Identity Matching Chains Protein Accession Entry Name
100.0 SERUM ALBUMIN P02768 ALBU_HUMAN
98.5 SERUM ALBUMIN Q5NVH5 ALBU_PONAB
93.7 Serum albumin A2V9Z4 ALBU_MACFA
93.7 Serum albumin Q28522 ALBU_MACMU