Regioselective Hydrolysis of Human Serum Albumin by ZrIV-Substituted Polyoxotungstates at the Interface of Positively Charged Protein Surface Patches and Negatively Charged Amino Acid Residues

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.

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

Proceedings of the National Academy of Sciences of Belarus Medical series ◽

10.29235/1814-6023-2021-18-1-46-57 ◽

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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Understanding the Regioselective Hydrolysis of Human Serum Albumin by Zr(IV)-Substituted Polyoxotungstates Using Tryptophan Fluorescence Spectroscopy

Inorganics ◽

10.3390/inorganics3020230 ◽

2015 ◽

Vol 3 (2) ◽

pp. 230-245 ◽

Cited By ~ 11

Author(s):

Vincent Goovaerts ◽

Karen Stroobants ◽

Gregory Absillis ◽

Tatjana Parac-Vogt

Keyword(s):

Human Serum Albumin ◽

Fluorescence Spectroscopy ◽

Serum Albumin ◽

Human Serum ◽

Tryptophan Fluorescence ◽

Hydrolysis Of ◽

Regioselective Hydrolysis

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

Biochemical Journal ◽

10.1042/bj2500443 ◽

1988 ◽

Vol 250 (2) ◽

pp. 443-446 ◽

Cited By ~ 11

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.

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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

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Modification of amino acid residues in human serum albumin by myeloperoxidase

Free Radical Biology and Medicine ◽

10.1016/j.freeradbiomed.2005.09.007 ◽

2006 ◽

Vol 40 (3) ◽

pp. 516-525 ◽

Cited By ~ 51

Author(s):

Pavel Salavej ◽

Holger Spalteholz ◽

Juergen Arnhold

Keyword(s):

Amino Acid ◽

Human Serum Albumin ◽

Serum Albumin ◽

Human Serum ◽

Amino Acid Residues

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Synthesis of conjugates of 1-(carboxymethyl)cytosine and 1-(5-O-carboxymethyl-β-D-arabinofuranosyl)cytosine with proteins

Collection of Czechoslovak Chemical Communications ◽

10.1135/cccc19793023 ◽

1979 ◽

Vol 44 (10) ◽

pp. 3023-3032 ◽

Cited By ~ 1

Author(s):

Helmut Pischel ◽

Antonín Holý ◽

Günther Wagner

Keyword(s):

Human Serum Albumin ◽

Acetic Anhydride ◽

Serum Albumin ◽

Human Serum ◽

Activated Esters ◽

Hydrolysis Of

1-(Carboxymethyl)cytosine (Ia), 1-(5-O-carboxymethyl-β-D-arabinofuranosyl)cytosine (IIa) and 5'-O-carboxylmethylcytidine (IIIa) were transformed by treatment with acetic anhydride and 4-dimethylaminopyridine to the peracetyl derivatives Ib-IIIb. These products reacted with p-nitrophenol in the presence of N, N'-dicyclohexylcarbodiimide to give the activated esters Ic-IIIc which on reaction with ammonia, dimethylamine or 2-aminoethanol afforded the corresponding carboxamides Id-IIId, IIe,f. Reactions of Ic and IIc with human serum albumin and bovine γ-globulin at pH 9.2, followed by hydrolysis of the N- or O-acetyl groups at pH 9.5, gave 50% up to 64% yields of the respective conjugates Ig, IIg and Ih, IIh.

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