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Title: Modulating Ligand Dissociation through Methyl Isomerism in Accessory Sites: Binding of Retinol to Cellular Carriers
Author: Estarellas, Carolina
Scaffidi, Salvatore
Saladino, Giorgio
Spyrakis, Francesca
Franzoni, Lorella
Galdeano Cantador, Carlos
Bidon-Chanal Badia, Axel
Gervasio, Francesco Luigi
Luque Garriga, F. Xavier
Keywords: Proteïnes
Isòmers òptics
Optical isomers
Issue Date: 12-Nov-2019
Publisher: American Chemical Society
Abstract: Due to the poor aqueous solubility of retinoids, evolution has tuned their binding to cellular proteins to address specialized physiological roles by modulating uptake, storage, and delivery to specific targets. With the aim to disentangle the structure-function relationships in these proteins and disclose clues for engineering selective carriers, the binding mechanism of the two most abundant retinol-binding isoforms was explored by using enhanced sampling molecular dynamics simulations and surface plasmon resonance. The distinctive dynamics of the entry portal site in the holo species was crucial to modulate retinol dissociation. Remarkably, this process is controlled at large extent by the replacement of Ile by Leu in the two isoforms, thus suggesting that a fine control of ligand release can be achieved through a rigorous selection of conservative mutations in accessory sites.
Note: Versió postprint del document publicat a:
It is part of: Journal of Physical Chemistry Letters, 2019, vol. 10, num. 23, p. 7333-7339
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ISSN: 1948-7185
Appears in Collections:Articles publicats en revistes (Institut de Biomedicina (IBUB))
Articles publicats en revistes (Farmàcia, Tecnologia Farmacèutica i Fisicoquímica)
Articles publicats en revistes (Nutrició, Ciències de l'Alimentació i Gastronomia)

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