Indomethacin Increases Quercetin Affinity for Human Serum Albumin: A Combined Experimental and Computational Study and Its Broader Implications

Human serum albumin (HSA) is the most abundant carrier protein in the human body. Competition for the same binding site between different ligands can lead to an increased active concentration or a faster elimination of one or both ligands. Indomethacin and quercetin both bind to the binding site located in the IIA subdomain. To determine the nature of the HSA-indomethacin-quercetin interactions, spectrofluorometric, docking, molecular dynamics studies, and quantum chemical calculations were performed. The results show that the indomethacin and quercetin binding sites do not overlap. Moreover, the presence of quercetin does not influence the binding constant and position of indomethacin in the pocket. However, binding of quercetin is much more favorable in the presence of indomethacin, with its position and interactions with HSA significantly changed. These results provide a new insight into drug-drug interactions, which can be important in situations when displacement from HSA or other proteins is undesirable or even desirable. This principle could also be used to deliberately prolong or shorten the xenobiotics’ half-life in the body, depending on the desired outcomes.

Download Full-text

Dansylation of human serum albumin in the study of the primary binding sites of bilirubin and l-tryptophan

Biochemical Journal ◽

10.1042/bj1810251 ◽

1979 ◽

Vol 181 (1) ◽

pp. 251-253 ◽

Cited By ~ 21

Author(s):

C Jacobsen ◽

J Jacobsen

Keyword(s):

Human Serum Albumin ◽

Serum Albumin ◽

Human Serum ◽

Binding Site ◽

Binding Sites ◽

Lysine Residue ◽

Bilirubin Binding ◽

Albumin Molecule ◽

Common Cavity

Binding of bilirubin and of L-tryptophan to dansylated albumins was investigated. Dansylation of less than one lysine residue per molecule of albumin did not affect the bilirubin binding, but decreased the L-tryptophan binding, indicating that dansylation had taken place in or near the l-tryptophan-binding site. Native albumin and albumin-bilirubin 1:1 complex showed the same affinity for L-tryptophan. The results indicate that, although L-tryptophan and bilirubin are bound in the same region, perhaps in a common cavity of the albumin molecule, such a cavity is sufficiently large to contain both ligands.

Download Full-text

Efficient identification of photolabelled amino acid residues by combining immunoaffinity purification with MS: revealing the semotiadil-binding site and its relevance to binding sites for myristates in domain III of human serum albumin

Biochemical Journal ◽

10.1042/0264-6021:3630223 ◽

2002 ◽

Vol 363 (2) ◽

pp. 223 ◽

Cited By ~ 3

Author(s):

Kohichi KAWAHARA ◽

Akihiko KUNIYASU ◽

Katsuyoshi MASUDA ◽

Masaji ISHIGURO ◽

Hitoshi NAKAYAMA

Keyword(s):

Amino Acid ◽

Human Serum Albumin ◽

Serum Albumin ◽

Human Serum ◽

Binding Site ◽

Binding Sites ◽

Amino Acid Residues ◽

Immunoaffinity Purification ◽

Domain Iii

Download Full-text

Allysine and α-Aminoadipic Acid as Markers of the Glyco-Oxidative Damage to Human Serum Albumin under Pathological Glucose Concentrations

Antioxidants ◽

10.3390/antiox10030474 ◽

2021 ◽

Vol 10 (3) ◽

pp. 474 ◽

Cited By ~ 1

Author(s):

Carolina Luna ◽

Alexis Arjona ◽

Carmen Dueñas ◽

Mario Estevez

Keyword(s):

Oxidative Stress ◽

Plasma Concentration ◽

Human Serum Albumin ◽

Serum Albumin ◽

Human Serum ◽

Typical Feature ◽

Advanced Glycation ◽

Chemical Mechanisms ◽

Fasting Plasma ◽

Insight Into

Understanding the molecular basis of the disease is of the utmost scientific interest as it contributes to the development of targeted strategies of prevention, diagnosis, and therapy. Protein carbonylation is a typical feature of glyco-oxidative stress and takes place in health disorders such as diabetes. Allysine as well as its oxidation product, the α-amino adipic acid (α-AA) have been found to be markers of diabetes risk whereas little is known about the chemistry involved in its formation under hyperglycemic conditions. To provide insight into this issue, human serum albumin was incubated in the presence of FeCl3 (25 μM) and increasing glucose concentrations for 32 h at 37 °C. These concentrations were selected to simulate (i) physiological fasting plasma concentration (4 mM), (ii) pathological pre-diabetes fasting plasma concentration (8 mM), and pathological diabetes fasting plasma concentration (12 mM) of glucose. While both allysine and α-AA were found to increase with increasing glucose concentrations, the carboxylic acid was only detected at pathological glucose concentrations and appeared to be a more reliable indicator of glyco-oxidative stress. The underlying chemical mechanisms of lysine glycation as well as of the depletion of tryptophan and formation of fluorescent and colored advanced glycation products are discussed.

Download Full-text

Mechanistic insight into the binding of graphene oxide with human serum albumin: Multispectroscopic and molecular docking approach

Spectrochimica Acta Part A Molecular and Biomolecular Spectroscopy ◽

10.1016/j.saa.2021.119750 ◽

2021 ◽

pp. 119750

Author(s):

Afroz Khan ◽

Fauzia Khan ◽

Moyad Shahwan ◽

Mohd Shahnawaz Khan ◽

Fohad Mabood Husain ◽

...

Keyword(s):

Graphene Oxide ◽

Molecular Docking ◽

Human Serum Albumin ◽

Serum Albumin ◽

Human Serum ◽

Mechanistic Insight ◽

Docking Approach ◽

Insight Into

Download Full-text

A Comprehensive Spectroscopic Analysis of the Ibuprofen Binding with Human Serum Albumin, Part II

Scientia Pharmaceutica ◽

10.3390/scipharm89030030 ◽

2021 ◽

Vol 89 (3) ◽

pp. 30

Author(s):

Anna Ploch-Jankowska ◽

Danuta Pentak ◽

Jacek E. Nycz

Keyword(s):

Fatty Acids ◽

Human Serum Albumin ◽

Serum Albumin ◽

Human Serum ◽

Tertiary Structure ◽

Temperature Characteristic ◽

The Body ◽

Structural Modifications ◽

Influence Of Temperature On ◽

Exogenous Substances

Human serum albumin (HSA) is the most abundant human plasma protein. HSA plays a crucial role in many binding endos- and exogenous substances, which affects their pharmacological effect. The innovative aspect of the study is not only the interaction of fatted (HSA) and defatted (dHSA) human serum albumin with ibuprofen (IBU), but the analysis of the influence of temperature on the structural modifications of albumin and the interaction between the drug and proteins from the temperature characteristic of near hypothermia (308 K) to the temperature reflecting inflammation in the body (312 K and 314 K). Ibuprofen is a non-steroidal anti-inflammatory drug. IBU is used to relieve acute pain, inflammation, and fever. To determine ibuprofen’s binding site in the tertiary structure of HSA and dHSA, fluorescence spectroscopy was used. On its basis, the fluorescent emissive spectra of albumin (5 × 10−6 mol/dm3) without and with the presence of ibuprofen (1 × 10−5–1 × 10−4 mol/dm3) was recorded. The IBU-HSA complex’s fluorescence was excited by radiation of wavelengths of λex 275 nm and λex 295 nm. Spectrophotometric spectroscopy allowed for recording the absorbance spectra (zero-order and second derivative absorption spectra) of HSA and dHSA under the influence of ibuprofen (1 × 10−4 mol/dm3). To characterize the changes of albumin structure the presence of IBU, circular dichroism was used. The data obtained show that the presence of fatty acids and human serum albumin temperature influences the strength and type of interaction between serum albumin and drug. Ibuprofen binds more strongly to defatted human serum albumin than to albumin in the presence of fatty acids. Additionally, stronger complexes are formed with increasing temperatures. The competitive binding of ibuprofen and fatty acids to albumin may influence the concentration of free drug fraction and thus its therapeutic effect.

Download Full-text