Characterization of site I of human serum albumin using spectroscopic analyses: Locational relations between regions Ib and Ic of site I

Yamasaki, Keishi; Maruyama, Toru; Takadate, Akira; Suenaga, Atsushi; Kragh‐Hansen, Ulrich; Otagiri, Masaki

doi:10.1002/jps.20203

Cited by 15 publications

(12 citation statements)

References 33 publications

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“…Additionally, at these high concentrations, contact quenching can also contribute to a fluorescence decrease, but at lower concentrations its effect is less pronounced. The obtained results are in accordance with results obtained by Zsila et al [18] and Dufour and Dangles [7], as well as with the crystallographic structures obtained by Petitpas et al [34] and Yamasaki et al [35,36], stating that the binding site in the subdomain IIA of HSA is large enough to accommodate multiple ligands at the same time. This was also confirmed for the case of interactions between warfarin and quercetin [29].…”

Section: Simultaneous Binding Of Indomethacin and Quercetin To Hsasupporting

confidence: 92%

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

Rimac

Tandarić

Vianello

et al. 2020

IJMS

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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.

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Section: Simultaneous Binding Of Indomethacin and Quercetin To Hsasupporting

confidence: 92%

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

Rimac

Tandarić

Vianello

et al. 2020

IJMS

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“…Our results—that flavonoids and warfarin do not share the same binding region—are consistent with results published by Zsila et al [ 28 ] and Dufour and Dangles [ 21 ]. Further support comes from crystallographic structures obtained by Petitpas et al [ 38 ] and research done by Yamasaki et al [ 43 , 45 ] stating that the IIA binding site can accommodate additional ligands in the warfarin vicinity. The difference in flavonoid fluorescence can be attributed to conformational and possible size changes of the IIA binding site caused by warfarin.…”

Section: Resultsmentioning

confidence: 84%

“…Additionally, Poór et al stated that the decrease of polarization values corresponds to higher rotational freedom of the free drug, i.e., displacement of warfarin from its albumin complex. As shown by Yamasaki et al [ 43 , 45 ], binding of a second ligand can influence the mobility of the first ligand and affect ICD and fluorescence anisotropy without displacement involved; changes in fluorescence anisotropy or induced circular dichroism do not unequivocally suggest ligand displacement. Additionally, the saturation transfer difference nuclear magnetic resonance (STD-NMR) technique used by Di Bari et al is characterized by the dependence of signal intensity on the proximity of ligand hydrogen atoms to HSA hydrogen atoms.…”

Section: Resultsmentioning

confidence: 99%

Warfarin and Flavonoids Do Not Share the Same Binding Region in Binding to the IIA Subdomain of Human Serum Albumin

et al. 2017

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Human serum albumin (HSA) binds a variety of xenobiotics, including flavonoids and warfarin. The binding of another ligand to the IIA binding site on HSA can cause warfarin displacement and potentially the elevation of its free concentration in blood. Studies dealing with flavonoid-induced warfarin displacement from HSA provided controversial results: estimated risk of displacement ranged from none to serious. To resolve these controversies, in vitro study of simultaneous binding of warfarin and eight different flavonoid aglycons and glycosides to HSA was carried out by fluorescence spectroscopy as well as molecular docking. Results show that warfarin and flavonoids do not share the same binding region in binding to HSA. Interactions were only observed at high warfarin concentrations not attainable under recommended dosing regimes. Docking experiments show that flavonoid aglycons and glycosides do not bind at warfarin high affinity sites, but rather to different regions within the IIA HSA subdomain. Thus, the risk of clinically significant warfarin–flavonoid interaction in binding to HSA should be regarded as negligible.

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“…higher rotational freedom of warfarin was taken as a proof of warfarin displacement. As shown by Yamasaki et al, 60 changes in rotational freedom are not necessarily equal to ligand displacement or binding. Similar reasoning can be applied in the case of formononetin.…”

Section: Determination Of Binding Constantsmentioning

confidence: 94%

Structural and electronic determinants of flavonoid binding to human serum albumin: an extensive ligand-based study

et al. 2016

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Characterization of site I of human serum albumin using spectroscopic analyses: Locational relations between regions Ib and Ic of site I

Cited by 15 publications

References 33 publications

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

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

Warfarin and Flavonoids Do Not Share the Same Binding Region in Binding to the IIA Subdomain of Human Serum Albumin

Structural and electronic determinants of flavonoid binding to human serum albumin: an extensive ligand-based study

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