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

1979 ◽  
Vol 181 (1) ◽  
pp. 251-253 ◽  
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.

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

2020 ◽  
Vol 21 (16) ◽  
pp. 5740
Author(s):  
Hrvoje Rimac ◽  
Tana Tandarić ◽  
Robert Vianello ◽  
Mirza Bojić
Keyword(s):  
Human Serum Albumin ◽  
Serum Albumin ◽  
Human Serum ◽  
Binding Site ◽  
Binding Sites ◽  
Quantum Chemical ◽  
Computational Study ◽  
The Body ◽  
Active Concentration ◽  
Insight Into

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.

scholarly journals 20: Mapping of the High-Affinity Bilirubin-Binding Site of Human Serum Albumin

1976 ◽  
Vol 10 (10) ◽  
pp. 876-876
Author(s):  
N Gitzelmann-Cumarasamy ◽  
C C Kuenzle ◽  
G Duc
Keyword(s):  
Human Serum Albumin ◽  
Serum Albumin ◽  
Human Serum ◽  
Binding Site ◽  
High Affinity ◽  
Bilirubin Binding

scholarly journals Effect of the binding of bilirubin to either the first class or the second class of binding sites of the human serum albumin molecule on its photochemical reaction

1989 ◽  
Vol 257 (3) ◽  
pp. 711-714 ◽  
Author(s):  
S Onishi ◽  
S Itoh ◽  
K Isobe ◽  
M Ochi ◽  
T Kunikata ◽  
...  
Keyword(s):  
Human Serum Albumin ◽  
Serum Albumin ◽  
Human Serum ◽  
Binding Sites ◽  
Serum Bilirubin ◽  
Bilirubin Concentration ◽  
Kinetics Of ◽  
Albumin Molecule ◽  
Human Serum Albumin Molecule ◽  
Serum Bilirubin Concentration

The kinetics of the photochemical changes of bilirubin were studied at a constant concentration of bilirubin bound either to the first class or to the second class of binding sites of the human serum albumin molecule. The more the bilirubin binds to the first class of binding sites in the human serum albumin molecule, the more readily geometric photoequilibrium to give (ZE)-bilirubin takes place. The more the bilirubin binds to the second class of binding sites or allosterically transformed binding sites induced by added SDS, the more readily structural photoisomerization, i.e. the formation of (EZ)-cyclobilirubin, takes place. When the serum bilirubin concentration is at low, safe, values bilirubin binds exclusively to the first class of binding sites and serves as an antioxidant [Onishi, Yamakawa & Ogawa (1971) Perinatology 1, 373-379]; at these concentrations human serum albumin protects bilirubin from irreversible photodegradation by only allowing readily reversible geometric photoisomerization. As the serum bilirubin concentration increases to high, and potentially dangerous, values, bilirubin binds to the second class of binding sites, and under these conditions human serum albumin seems to promote the photocyclization of bilirubin. During irradiation human serum albumin seems to act by retaining low, useful, concentrations of bilirubin while facilitating irreversible photoisomerization of excess bilirubin.

scholarly journals Influence of mutations caused by radiation exposure on the bilirubin binding sites of human serum albumin

2021 ◽  
Vol 18 (1) ◽  
pp. 46-57
Author(s):  
V. V. Poboinev ◽  
V. V. Khrustalev ◽  
A. N. Stojarov ◽  
T. A. Khrustaleva
Keyword(s):  
Amino Acid ◽  
Secondary Structure ◽  
Human Serum Albumin ◽  
Serum Albumin ◽  
Radiation Exposure ◽  
Human Serum ◽  
Binding Sites ◽  
Amino Acid Substitutions ◽  
Amino Acid Residues ◽  
Bilirubin Binding

In this article we analyze the bilirubin binding sites of human serum albumin from the point of view of the secondary structure instability, as well as the effect of amino acid substitutions caused by radiation exposure on the ability of albumin to bind bilirubin-IX-alpha. Based on calculations of binding energy and inhibition constants of bilirubin-albumin complexes before and after the amino acid substitutions, it was found that amino acid substitutions have different effects on the ability of human serum albumin to bind bilirubin. Amino acid substitutions Asp269-Gly269 (Nagasaki-1), Glu354-Lys354 (Hiroshima-1), Asp375-Asn375 (Nagasaki-2) reduce the binding free energy of bilirubin with human serum albumin, and the amino acid substitutions His3-Gln3 (Nagasaki-3) and Glu382-Lys382 (Hiroshima-2) increase it during molecular docking with the corresponding areas of the protein surface. The inhibition constants are significantly higher than with known binding sites. In general, mutations caused by radiation exposure cannot effect on bilirubin binding sites of human serum albumin, since the amino acid residues that are replaced do not interact with the amino acid residues from the binding sites (Leu115, Arg117, Phe134, Tyr138, Ile142, Phe149, Phe157, Tyr161, Arg186, Lys190, Lys240, Arg222). All amino acid residues from known binding sites are located in stable elements of the secondary structure of human serum albumin.The data obtained are important for understanding the impact of radiation exposure on the development of bilirubin encephalopathy in the population of the Chernobyl region and Japan.

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