Next Article in Journal
Carboxamide Derivatives Are Potential Therapeutic AHR Ligands for Restoring IL-4 Mediated Repression of Epidermal Differentiation Proteins
Previous Article in Journal
Molecular Docking and Molecular Dynamics Simulations Discover Curcumin Analogue as a Plausible Dual Inhibitor for SARS-CoV-2
Previous Article in Special Issue
Variations in the Human Serum Albumin Gene: Molecular and Functional Aspects
 
 
Article

Structural Analysis of Human Serum Albumin in Complex with the Fibrate Drug Gemfibrozil

1
Department of Biology, University of Padua, Viale G. Colombo 3, 35131 Padua, Italy
2
Department of Molecular Sciences and Nanosystems, Ca’ Foscari University of Venice, Via Torino 155, 30172 Mestre, Italy
3
Department of Medicine, Unit of Andrology and Reproductive Medicine, University of Padova, Via Giustiniani 2, 35128 Padova, Italy
4
European Centre for Living Technology (ECLT), Ca’ Bottacin, Dorsoduro 3911, Calle Crosera, 30123 Venice, Italy
*
Authors to whom correspondence should be addressed.
The authors contributed equally to this work.
Present address: The Armenise-Harvard Laboratory of Structural Biology, Department of Biology and Biotechnology “L. Spallanzani”, University of Pavia, Via Ferrata 9, 27100 Pavia, Italy.
Academic Editor: Saša Frank
Int. J. Mol. Sci. 2022, 23(3), 1769; https://doi.org/10.3390/ijms23031769
Received: 30 December 2021 / Revised: 28 January 2022 / Accepted: 31 January 2022 / Published: 4 February 2022
Gemfibrozil (GEM) is an orally administered lipid-regulating fibrate derivative drug sold under the brand name Lopid®, among others. Since its approval in the early 80s, GEM has been largely applied to treat hypertriglyceridemia and other disorders of lipid metabolism. Though generally well tolerated, GEM can alter the distribution and the free, active concentration of some co-administered drugs, leading to adverse effects. Most of them appear to be related to the ability of GEM to bind with high affinity human serum albumin (HSA), the major drug-carrier protein in blood plasma. Here, we report the crystal structure of HSA in complex with GEM. Two binding sites have been identified, namely Sudlow’s binding sites I (FA7) and II (FA3–FA4). A comparison of the crystal structure of HSA in complex with GEM with those of other previously described HSA–drug complexes enabled us to appreciate the analogies and differences in their respective binding modes. The elucidation of the molecular interaction between GEM and HSA might offer the basis for the development of novel GEM derivatives that can be safely and synergistically co-administered with other drugs, enabling augmented therapeutic efficacies. View Full-Text
Keywords: gemfibrozil; fibric acid; fibrate; Lopid; serum albumin; Sudlow’s site; hypolipidemic drug; hyperlipidaemia; hypertriglyceridemia; hypercholesterolemia gemfibrozil; fibric acid; fibrate; Lopid; serum albumin; Sudlow’s site; hypolipidemic drug; hyperlipidaemia; hypertriglyceridemia; hypercholesterolemia
Show Figures

Figure 1

MDPI and ACS Style

Liberi, S.; Linciano, S.; Moro, G.; De Toni, L.; Cendron, L.; Angelini, A. Structural Analysis of Human Serum Albumin in Complex with the Fibrate Drug Gemfibrozil. Int. J. Mol. Sci. 2022, 23, 1769. https://doi.org/10.3390/ijms23031769

AMA Style

Liberi S, Linciano S, Moro G, De Toni L, Cendron L, Angelini A. Structural Analysis of Human Serum Albumin in Complex with the Fibrate Drug Gemfibrozil. International Journal of Molecular Sciences. 2022; 23(3):1769. https://doi.org/10.3390/ijms23031769

Chicago/Turabian Style

Liberi, Stefano, Sara Linciano, Giulia Moro, Luca De Toni, Laura Cendron, and Alessandro Angelini. 2022. "Structural Analysis of Human Serum Albumin in Complex with the Fibrate Drug Gemfibrozil" International Journal of Molecular Sciences 23, no. 3: 1769. https://doi.org/10.3390/ijms23031769

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop