scholarly journals The fatty-acid-induced conformational states of human serum albumin investigated by means of multiple co-binding of protons and oleic acid

1988 ◽  
Vol 250 (2) ◽  
pp. 443-446 ◽  
Author(s):  
J H M Dröge ◽  
L H M Janssen ◽  
J Wilting
Keyword(s):  
Oleic Acid ◽  
Fatty Acid ◽  
Amino Acid ◽  
Human Serum Albumin ◽  
Serum Albumin ◽  
Human Serum ◽  
Binding Sites ◽  
Conformational Transitions ◽  
Amino Acid Residues ◽  
Ph Stat

The binding of oleic acid to human serum albumin causes progressive changes in (a) the pK of some amino acid residues, as detected by pH-stat titration and (b) the induced molar ellipticities of albumin-bound drugs (diazepam and oxyphenbutazone), as measured by c.d. It is concluded that albumin undergoes several conformational transitions as the amount of oleic acid bound increases from 0 to about 9 molecules/molecule of protein. At least three different conformations of the protein seem to be involved. These conformations can be linked with the three classes of oleic acid-binding sites on albumin.

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.

scholarly journals Oxidative Alteration of Trp-214 and Lys-199 in Human Serum Albumin Increases Binding Affinity with Phenylbutazone: A Combined Experimental and Computational Investigation

2018 ◽  
Vol 19 (10) ◽  
pp. 2868 ◽  
Author(s):  
Luiza Bertozo ◽  
Ernesto Tavares Neto ◽  
Leandro Oliveira ◽  
Valdecir Ximenes
Keyword(s):  
Amino Acid ◽  
Human Serum Albumin ◽  
Serum Albumin ◽  
Human Serum ◽  
Interaction Energy ◽  
Score Function ◽  
Oxidation Products ◽  
Amino Acid Residues ◽  
Computational Investigation ◽  
A Current

Human serum albumin (HSA) is a target for reactive oxygen species (ROS), and alterations of its physiological functions caused by oxidation is a current issue. In this work, the amino-acid residues Trp-214 and Lys-199, which are located at site I of HSA, were experimentally and computationally oxidized, and the effect on the binding constant with phenylbutazone was measured. HSA was submitted to two mild oxidizing reagents, taurine monochloramine (Tau-NHCl) and taurine dibromamine (Tau-NBr2). The oxidation of Trp-214 provoked spectroscopic alterations in the protein which were consistent with the formation of N′-formylkynurenine. It was found that the oxidation of HSA by Tau-NBr2, but not by Tau-NHCl, provoked a significant increase in the association constant with phenylbutazone. The alterations of Trp-214 and Lys-199 were modeled and simulated by changing these residues using the putative oxidation products. Based on the Amber score function, the interaction energy was measured, and it showed that, while native HSA presented an interaction energy of −21.3 kJ/mol, HSA with Trp-214 altered to N′-formylkynurenine resulted in an energy of −28.4 kJ/mol, and HSA with Lys-199 altered to its carbonylated form resulted in an energy of −33.9 kJ/mol. In summary, these experimental and theoretical findings show that oxidative alterations of amino-acid residues at site I of HSA affect its binding efficacy.

scholarly journals Effects of fatty acid on the specific drug-binding sites of human serum albumin.

1986 ◽  
Vol 34 (8) ◽  
pp. 3394-3402 ◽  
Author(s):  
KAZUO MARUYAMA ◽  
SHOJI AWAZU ◽  
HIDEO NISHIGORI ◽  
MOTOHARU IWATSURU
Keyword(s):  
Fatty Acid ◽  
Human Serum Albumin ◽  
Serum Albumin ◽  
Human Serum ◽  
Binding Sites ◽  
Drug Binding ◽  
Specific Drug ◽  
Drug Binding Sites

scholarly journals Evidence that Chemical Chaperone 4-Phenylbutyric Acid Binds to Human Serum Albumin at Fatty Acid Binding Sites

PLoS ONE ◽  
2015 ◽  
Vol 10 (7) ◽  
pp. e0133012 ◽  
Author(s):  
Debasish Roy ◽  
Vinod Kumar ◽  
Joel James ◽  
Mohamed Sham Shihabudeen ◽  
Shweta Kulshrestha ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Human Serum Albumin ◽  
Serum Albumin ◽  
Human Serum ◽  
Binding Sites ◽  
Chemical Chaperone ◽  
Fatty Acid Binding ◽  
Phenylbutyric Acid

scholarly journals Localizing Fatty Acid Binding Sites on Human Serum Albumin by 2D-NMR

2009 ◽  
Vol 96 (3) ◽  
pp. 442a
Author(s):  
Eileen Krenzel ◽  
Zhongjing Chen ◽  
James A. Hamilton
Keyword(s):  
Fatty Acid ◽  
Human Serum Albumin ◽  
Serum Albumin ◽  
Human Serum ◽  
Binding Sites ◽  
2D Nmr ◽  
Fatty Acid Binding
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