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Structural stability, acidity, and halide selectivity of the fluoride riboswitch recognition site

Using static and dynamics DFT methods we show that the Mg2+/F-/phosphate/water cluster at the center of the fluoride riboswitch is stable by its own and, once assembled, does not rely on any additional factor from the overall RNA fold. Further, we predict that the pKa of the water molecule bridging two Mg cations is around 8.4. We also demonstrate that the halide selectivity of the fluoride riboswitch is determined by the stronger Mg-F bond, which is capable of keeping together the cluster. Replacing F- with Cl- results in a cluster that is unstable under dynamic conditions. Similar conclusions on the structure and energetics of the cluster in the binding pocket of fluoride-inhibited pyrophosphatase suggest that the peculiarity of fluoride is in its ability to establish much stronger metal-halide bonds

A.P. thanks the Spanish MINECO for a Ramón y Cajal contract (RYC-2009-05226) and European Commission for a Career Integration Grant (CIG09-GA-2011-293900).

© Journal of the American Chemical Society, 2015, vol. 137, núm. 1, p. 299-306

American Chemical Society (ACS)

Author: Chawla, Mohit
Credendino, Raffaele
Poater Teixidor, Albert
Oliva, Romina
Cavallo, Luigi
Date: 2015 January 14
Abstract: Using static and dynamics DFT methods we show that the Mg2+/F-/phosphate/water cluster at the center of the fluoride riboswitch is stable by its own and, once assembled, does not rely on any additional factor from the overall RNA fold. Further, we predict that the pKa of the water molecule bridging two Mg cations is around 8.4. We also demonstrate that the halide selectivity of the fluoride riboswitch is determined by the stronger Mg-F bond, which is capable of keeping together the cluster. Replacing F- with Cl- results in a cluster that is unstable under dynamic conditions. Similar conclusions on the structure and energetics of the cluster in the binding pocket of fluoride-inhibited pyrophosphatase suggest that the peculiarity of fluoride is in its ability to establish much stronger metal-halide bonds
A.P. thanks the Spanish MINECO for a Ramón y Cajal contract (RYC-2009-05226) and European Commission for a Career Integration Grant (CIG09-GA-2011-293900).
Format: application/pdf
ISSN: 0002-7863 (versió paper)
1520-5126 (versió electrònica)
Document access: http://hdl.handle.net/10256/13301
Language: eng
Publisher: American Chemical Society (ACS)
Collection: MINECO/PN 2012-2015/RYC-2009-05226
Reproducció digital del document publicat a: http://dx.doi.org/10.1021/ja510549b
Articles publicats (D-Q)
info:eu-repo/grantAgreement/EC/FP7/293900
Is part of: © Journal of the American Chemical Society, 2015, vol. 137, núm. 1, p. 299-306
Rights: Tots els drets reservats
Subject: Funcional de densitat, Teoria del
Density functionals
Title: Structural stability, acidity, and halide selectivity of the fluoride riboswitch recognition site
Type: info:eu-repo/semantics/article
Repository: DUGiDocs

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