Estarellas, C;
Scaffidi, S;
Saladino, G;
Spyrakis, F;
Franzoni, L;
Galdeano, C;
Bidon-Chanal, A;
... Luque, FJ; + view all
(2019)
Modulating Ligand Dissociation Through Methyl Isomerism in Accessory Sites: Binding of Retinol to Cellular Carriers.
The Journal of Physical Chemistry Letters
, 10
(23)
pp. 7333-7339.
10.1021/acs.jpclett.9b02861.
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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 to a large extent by the replacement of Ile by Leu in the two isoforms, thus suggesting that fine control of ligand release can be achieved through a rigorous selection of conservative mutations in accessory sites.
| Type: | Article |
|---|---|
| Title: | Modulating Ligand Dissociation Through Methyl Isomerism in Accessory Sites: Binding of Retinol to Cellular Carriers |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1021/acs.jpclett.9b02861 |
| Publisher version: | https://doi.org/10.1021/acs.jpclett.9b02861 |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | Entropy, Elements, Free energy, Ligands, Genetics |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > UCL BEAMS UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences > Dept of Chemistry |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10086909 |
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