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

2005 ◽  
Vol 387 (3) ◽  
pp. 695-702 ◽  
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.

Mixed Micells: A New Problem-Free Solution for co-123I-Heptadecanoic Acid in Comparison

1984 ◽  
Vol 22 (01) ◽  
pp. 27-28
Author(s):  
M. Argentini ◽  
P. Bläuenstein ◽  
R. Lerch ◽  
P. A. Schubiger
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Human Serum Albumin ◽  
Serum Albumin ◽  
Human Serum ◽  
Adverse Reactions ◽  
Tween 80 ◽  
Good Stability ◽  
Heptadecanoic Acid ◽  
Free Solution

SummaryThe most commonly used reagents for solubilization of 123I fatty acids have very serious drawbacks. Human serum albumin solubilizes the fatty acid only slowly and TWEEN 80 is not free of stability problems. Furthermore adverse reactions in human applications cannot be excluded. In comparison, the newly introduced mixed micells look very favourable: fast solubilization, good stability and no adverse reactions. Biodistribution experiments on rats show an adequate performance of the micells. Hitherto this solution has been applied in more than 200 patients without any complication.

scholarly journals Albumin-mediated alteration of plasma zinc speciation by fatty acids modulates blood clotting in type-2 diabetes

2021 ◽  
Author(s):  
Amélie I. S. Sobczak ◽  
Kondwani G. H. Katundu ◽  
Fladia A. Phoenix ◽  
Siavash Khazaipoul ◽  
Ruitao Yu ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Fatty Acids ◽  
Fatty Acid ◽  
Human Serum Albumin ◽  
Serum Albumin ◽  
Human Serum ◽  
Blood Clotting ◽  
Plasma Zinc ◽  
Zinc Speciation

Zn2+ is an essential regulator of coagulation. In plasma, Zn2+ availability is fine-tuned by human serum albumin (HSA). Here we show that elevated fatty acid levels contribute to altered coagulation in type-2 diabetes through Zn2+ mishandling by HSA.

THE EFFECT OF FREE FATTY ACIDS ON RESIN UPTAKE OF TRI-IODOTHYRONINE FROM HUMAN, RAT, RABBIT AND GUINEA-PIG SERUM AND HUMAN SERUM ALBUMIN

1969 ◽  
Vol 45 (4) ◽  
pp. 489-493 ◽  
Author(s):  
P. W. NATHANIELSZ
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Free Fatty Acid ◽  
Human Serum Albumin ◽  
Guinea Pig ◽  
Serum Albumin ◽  
Free Fatty Acids ◽  
Human Serum ◽  
Rat Serum ◽  
Pig Serum

SUMMARY Recently changes in plasma free fatty acids have been suggested as a possible regulator of the levels of free thyroxine in the plasma. Oleic acid has been shown to displace tri-iodothyronine from human serum, human serum albumin, rat serum, rabbit serum and guinea-pig serum. The extent of the displacement, much greater from human serum albumin than from whole serum, suggests that free fatty acid does not affect the globulin binding site. It would also appear that, in the rat, all the binding sites are sensitive to free fatty acids and hence there is probably only albumin binding in this species. The results with rabbit and guinea-pig serum were intermediate to those with human and rat serum. A significant rise in resin uptake of tri-iodothyronine in vitro occurred with an increase of free fatty acid level of 0·5 m-equiv./l., well within the physiological range.

scholarly journals Conformational changes in human serum albumin studied by fluorescence and absorption spectroscopy. Distance measurements as a function of pH and fatty acids

1989 ◽  
Vol 258 (1) ◽  
pp. 199-204 ◽  
Author(s):  
B Honoré ◽  
A O Pedersen
Keyword(s):  
Fatty Acids ◽  
Human Serum Albumin ◽  
Serum Albumin ◽  
Human Serum ◽  
Conformational Changes ◽  
Saturated Fatty Acids ◽  
Distance Measurements ◽  
Low Concentrations ◽  
Long Chain ◽  
Chain Fatty Acids

pH- and fatty acid-induced conformational changes in human serum albumin were investigated by fluorescence-energy transfer, determining the distance between Trp-214 and bound bilirubin at 25 degrees C. This distance changes significantly with the pH, being 2.52 +/- 0.01 nm at pH 6, 2.31 +/- 0.04 nm at pH 9, 2.13 +/- 0.07 nm at pH 11.0 and 2.77 nm at pH 11.9. The influence of different fatty acids on the distance was also determined. At pH 7.4 medium-chain fatty acids seem to increase this distance, whereas long-chain fatty acids, at low concentrations, decrease the distance between the two chromophores. The contraction of the protein carrying long-chain saturated fatty acids is even more pronounced at pH 9.

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

Molecules ◽  
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.

scholarly journals Blind testing cross-linking/mass spectrometry under the auspices of the 11th critical assessment of methods of protein structure prediction (CASP11)

2016 ◽  
Author(s):  
Adam Belsom ◽  
Michael Schneider ◽  
Lutz Fischer ◽  
Oliver Brock ◽  
Juri Rappsilber
Keyword(s):  
Mass Spectrometry ◽  
Protein Structure ◽  
Human Serum Albumin ◽  
Serum Albumin ◽  
Human Serum ◽  
Protein Structure Prediction ◽  
Structure Prediction ◽  
Critical Assessment ◽  
Conformational Space ◽  
Cross Linking

SummaryDetermining the structure of a protein by any method requires varies contributions from experimental and computational sides. In a recent study, high-density cross-linking/mass spectrometry data in combination with ab initio structure prediction by conformational space search determined the structure of human serum albumin (HSA) domains, with an RMSD to X-ray structure of up to 2.53 Å, or 3.38 Å in the context of blood serum. This paper reports the blind test on the readiness of this technology through the help of Critical Assessment of protein Structure Prediction (CASP). We identified between 201-381 unique residue pairs at an estimated 5% FDR (at link level albeit with missing site assignment precision evaluation), for the four proteins that we provided data for. This equates to between 0.63-1.20 proximal residues per residue, which is comparable to that obtained in the HSA study (0.85 links per residue at 5% FDR). Nevertheless, initial results of CASP11 have suggested that improvements in structure prediction using cross-link data are slight. Most significantly, however, CASP11 revealed to us some of the current limitations of cross-linking, spelling out areas in which the method must develop in future: links spread unevenly over sequence and beta sheets both lacked links and suffered from weak definition of observed links over structure. With CASP12 taking place this year and biannually in the future, blind testing low-resolution structure analysis tools is a worthwhile and feasible undertaking. Data are available via ProteomeXchange with identifier PXD003643.The abbreviations used areCLMScross-linking/mass spectrometry;NHSN-hydroxysuccinimide;NMRnuclear magnetic resonance;sulfo-SDAsulfo-NHSdiazirine, sulfosuccinimidyl 4,4’-azipentanoate;FDRfalse discovery rate;MBSmodel-based search;HSAhuman serum albumin;RMSDroot-mean-square deviation;CASPCritical Assessment of protein Structure Prediction;Tristris(hydroxymethyl)aminomethane;PESpolyethersulphone;IAAiodoacetamide;LTQlinear trap quadrupole;MS2tandem MS scan;LC-MSliquid chromatography mass spectrometry;FMfree modelling.

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