The THE ROLE OF ASTAXANTHIN COMPARED WITH METFORMIN IN PREVENTING GLYCATED HUMAN SERUM ALBUMIN FROM POSSIBLE UNFOLDING: A MOLECULAR DYNAMIC STUDY

Objectives: Albumin in diabetes mellitus undergoes conformational changes that affect the ability as an endogenous scavenger. Treatment with astaxanthin (ASX) expected to improve the function of albumin in case of diabetes mellitus. The objectives of this study are to compare the capability of ASX and metformin to prevent conformational changes on glycated albumin. Methods: Data mining is performed to obtain human serum albumin (HSA) (4K2C), glucose (79025), ASX (5281224), and metformin (4091). Data preparation used PyRx and Discovery Studio 2016 Client. PyRx is utilized for docking and analysis of receptor-ligand interactions with LigPlus and Discovery Studio 2016 Client. YASARA is used for molecular dynamics simulations with a running time of 15.000 ps. Results: A description of the glycated-HSA (gHSA) conformational changes that are bound to metformin has been successfully carried out. Changes that occur were unfolding and release of bonds in gHSA. Unfolding on gHSA includes the release of bonds between sites A and B. The root mean square deviation (RMSD) backbone value of metformin-gHSA shows a significant difference with gHSA at 8650 ps where gHSA showed 6.47 nm while the metformin-gHSA was 8.06 nm and continues to increase up to 15.72 nm at the end of the simulation. RMSD and root mean square fluctuation residues of gHSA which were interacted with ASX showed conditions close to normal HSA. In 11725 ps ASX-gHSA remained stable at 5.78 nm, whereas gHSA increased to 8.13 nm. gHSA at the end of the simulation showed a number of 9.052 nm while the normal HSA was 7.561 nm. Conclusion: This result indicated that ASX prevents gHSA from possible unfolding.

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Changes in Glycated Human Serum Albumin Binding Affinity for Losartan in the Presence of Fatty Acids In Vitro Spectroscopic Analysis

Molecules ◽

10.3390/molecules27020401 ◽

2022 ◽

Vol 27 (2) ◽

pp. 401

Author(s):

Agnieszka Szkudlarek ◽

Jadwiga Pożycka ◽

Karolina Kulig ◽

Aleksandra Owczarzy ◽

Wojciech Rogóż ◽

...

Keyword(s):

Fatty Acids ◽

Human Serum Albumin ◽

Serum Albumin ◽

Human Serum ◽

Conformational Changes ◽

Specific Binding ◽

Physiological State ◽

Glycated Albumin ◽

The Body ◽

Angiotensin Ii Receptor

Conformational changes in human serum albumin due to numerous modifications that affect its stability and biological activity should be constantly monitored, especially in elderly patients and those suffering from chronic diseases (which include diabetes, obesity, and hypertension). The main goal of this study was to evaluate the effect of a mixture of fatty acids (FA) on the affinity of losartan (LOS, an angiotensin II receptor (AT1) blocker used in hypertension, a first-line treatment with coexisting diabetes) for glycated albumin—simulating the state of diabetes in the body. Individual fatty acid mixtures corresponded to the FA content in the physiological state and in various clinical states proceeding with increased concentrations of saturated (FAS) and unsaturated (FAUS) acids. Based on fluorescence studies, we conclude that LOS interacts with glycated human serum albumin (af)gHSA in the absence and in the presence of fatty acids ((af)gHSAphys, (af)gHSA4S, (af)gHSA8S, (af)gHSA4US, and (af)gHSA8US) and quenches the albumin fluorescence intensity via a static quenching mechanism. LOS not only binds to its specific binding sites in albumins but also non-specifically interacts with the hydrophobic fragments of its surface. Incorrect contents of fatty acids in the body affect the drug pharmacokinetics. A higher concentration of both FAS and FAUS acids in glycated albumin reduces the stability of the complex formed with losartan. The systematic study of FA and albumin interactions using an experimental model mimicking pathological conditions in the body may result in new tools for personalized pharmacotherapy.

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Increased oxidized form of human serum albumin in patients with diabetes mellitus

Diabetes Research and Clinical Practice ◽

10.1016/0168-8227(92)90140-m ◽

1992 ◽

Vol 18 (3) ◽

pp. 153-158 ◽

Cited By ~ 69

Author(s):

Eiji Suzuki ◽

Keigo Yasuda ◽

Noriyuki Takeda ◽

Shigeki Sakata ◽

Seiichi Era ◽

...

Keyword(s):

Diabetes Mellitus ◽

Human Serum Albumin ◽

Serum Albumin ◽

Human Serum ◽

Patients With Diabetes

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Spectroscopic and molecular docking studies for characterizing binding mechanism and conformational changes of human serum albumin upon interaction with Telmisartan

Saudi Pharmaceutical Journal ◽

10.1016/j.jsps.2020.04.015 ◽

2020 ◽

Vol 28 (6) ◽

pp. 729-736

Author(s):

Mohammed Al bratty

Keyword(s):

Molecular Docking ◽

Human Serum Albumin ◽

Serum Albumin ◽

Human Serum ◽

Conformational Changes ◽

Docking Studies ◽

Binding Mechanism ◽

Molecular Docking Studies

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Binding Interactions and Conformational Changes Induced by Sulfonated Aluminum Phthalocyanines in Human Serum Albumin

Archives of Biochemistry and Biophysics ◽

10.1006/abbi.1999.1174 ◽

1999 ◽

Vol 366 (1) ◽

pp. 21-30 ◽

Cited By ~ 29

Author(s):

Tsvetan G. Gantchev ◽

René Ouellet ◽

Johan E. van Lier

Keyword(s):

Human Serum Albumin ◽

Serum Albumin ◽

Human Serum ◽

Conformational Changes ◽

Binding Interactions

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Human Serum Albumin Conformational Changes as Induced by Tenoxicam and Modified by Simultaneous Diazepam Binding

Journal of Pharmacy and Pharmacology ◽

10.1111/j.2042-7158.1993.tb07179.x ◽

1993 ◽

Vol 45 (12) ◽

pp. 1050-1053 ◽

Cited By ~ 14

Author(s):

F. BRÉE ◽

S. URIEN ◽

P. NGUYEN ◽

J. P. TILLEMENT ◽

A. STEINER ◽

...

Keyword(s):

Human Serum Albumin ◽

Serum Albumin ◽

Human Serum ◽

Conformational Changes

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Systematic FTIR Spectroscopy Study of the Secondary Structure Changes in Human Serum Albumin under Various Denaturation Conditions

Biomolecules ◽

10.3390/biom9080359 ◽

2019 ◽

Vol 9 (8) ◽

pp. 359 ◽

Cited By ~ 22

Author(s):

Usoltsev ◽

Sitnikova ◽

Kajava ◽

Uspenskaya

Keyword(s):

Secondary Structure ◽

Human Serum Albumin ◽

Serum Albumin ◽

Human Serum ◽

Ftir Spectroscopy ◽

Conformational Changes ◽

Data Interpretation ◽

Random Coil ◽

Helical Conformation ◽

Structure Changes

Human serum albumin (HSA) is the most abundant protein in blood plasma. HSA is involved in the transport of hormones, fatty acids, and some other compounds, maintenance of blood pH, osmotic pressure, and many other functions. Although this protein is well studied, data about its conformational changes upon different denaturation factors are fragmentary and sometimes contradictory. This is especially true for FTIR spectroscopy data interpretation. Here, the effect of various denaturing agents on the structural state of HSA by using FTIR spectroscopy in the aqueous solutions was systematically studied. Our data suggest that the second derivative deconvolution method provides the most consistent interpretation of the obtained IR spectra. The secondary structure changes of HSA were studied depending on the concentration of the denaturing agent during acid, alkaline, and thermal denaturation. In general, the denaturation of HSA in different conditions is accompanied by a decrease in α-helical conformation and an increase in random coil conformation and the intermolecular β-strands. Meantime, some variation in the conformational changes depending on the type of the denaturation agent were also observed. The increase of β-structural conformation suggests that HSA may form amyloid-like aggregates upon the denaturation.

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Calcium ion binding to clinically relevant chemical modifications of human serum albumin

Clinical Chemistry ◽

10.1093/clinchem/41.11.1654 ◽

1995 ◽

Vol 41 (11) ◽

pp. 1654-1661 ◽

Cited By ~ 16

Author(s):

H Vorum ◽

K Fisker ◽

M Otagiri ◽

A O Pedersen ◽

U Kragh-Hansen

Keyword(s):

Human Serum Albumin ◽

Serum Albumin ◽

Human Serum ◽

Conformational Changes ◽

Calcium Binding ◽

Equilibrium Dialysis ◽

Thiol Group ◽

Protein Molecule ◽

Penicillin G ◽

Lysine Residues

Abstract Calcium binding to glycated, penicilloylated, acetylated, and normal defatted human serum albumin as well as to mercapt- and nonmercaptalbumin was studied by equilibrium dialysis of radioactive Ca2+. Binding was quantified by five Scatchard constants [ni = 1, (i = 1-4) and n5 = 10]. Glycation resulted in increased k1- and k2-values and unchanged k3-k5-values, whereas penicilloylation increased all five association constants. The increments were greater the more pronounced the modification, and the enhancements caused by penicilloylation were, for the same degree of modification, greater than those produced by glycation. In contrast, acetylation by acetylsalicylate did not affect calcium binding. Likewise, binding to mercapt- and nonmercaptalbumin was the same, a finding showing that the thiol group of cysteine 34 is not important for calcium binding. D-Glucose and penicillin G are known to react with lysine residues of albumin, and the enhancement of binding resulting from glycation or penicilloylation is probably brought about by unspecific electrostatic effects, possibly supplemented by conformational changes of the protein molecule. The relative importance of the three domains of human serum albumin for calcium binding is discussed.

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Enhanced nonenzymatic glucosylation of human serum albumin in diabetes mellitus.

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.76.9.4258 ◽

1979 ◽

Vol 76 (9) ◽

pp. 4258-4261 ◽

Cited By ~ 190

Author(s):

C. E. Guthrow ◽

M. A. Morris ◽

J. F. Day ◽

S. R. Thorpe ◽

J. W. Baynes

Keyword(s):

Diabetes Mellitus ◽

Human Serum Albumin ◽

Serum Albumin ◽

Human Serum

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Probing conformational changes of human serum albumin due to unsaturated fatty acid binding by chemical cross-linking and mass spectrometry

Biochemical Journal ◽

10.1042/bj20041624 ◽

2005 ◽

Vol 387 (3) ◽

pp. 695-702 ◽

Cited By ~ 48

Author(s):

Bill X. HUANG ◽

Chhabil DASS ◽

Hee-Yong KIM

Keyword(s):

Mass Spectrometry ◽

Fatty Acids ◽

Fatty Acid ◽

Human Serum Albumin ◽

Serum Albumin ◽

Human Serum ◽

Conformational Changes ◽

Cross Linking ◽

X Ray ◽

Chemical Cross Linking

Mass spectrometry with chemical cross-linking was used to probe the conformational changes of HSA (human serum albumin) in solution on interaction with monounsaturated OA (oleic acid) or polyunsaturated AA (arachidonic acid) or DHA (docosahexaenoic acid). Fatty acid-free or -bound HSA was modified with lysine-specific cross-linkers and digested with trypsin. Cross-linked peptides were analysed by nano-electrospray ionization MS to localize the sites of cross-linking. Our data indicated that a local conformational change involving movement of the side chains of Lys-402 of subdomain IIIA or Lys-541 of subdomain IIIB occurred upon binding of all three fatty acids. Our data also indicated that the side chains of Lys-205 (IIA) and Lys-466 (IIIA) moved closer towards each other upon binding AA or DHA, but not OA, suggesting that the conformations of HSA when bound to mono- and poly-unsaturated fatty acids are distinctively different. While these observations agreed with previous X-ray crystallographic studies, the distances between ε-amino groups of most cross-linked lysine pairs were shorter than the crystal structure predicted, possibly reflecting a discrepancy between the solution and crystal structures. This method can serve as a useful complement to X-ray crystallography, particularly in probing the structure of a protein in solution.

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