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

Handle URI:
http://hdl.handle.net/10754/564011
Title:
Structural stability, acidity, and halide selectivity of the fluoride riboswitch recognition site
Authors:
Chawla, Mohit; Credendino, Raffaele; Poater, Albert; Oliva, Romina M.; Cavallo, Luigi ( 0000-0002-1398-338X )
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.
KAUST Department:
KAUST Catalysis Center (KCC); Physical Sciences and Engineering (PSE) Division; Chemical Science Program
Publisher:
American Chemical Society (ACS)
Journal:
Journal of the American Chemical Society
Issue Date:
14-Jan-2015
DOI:
10.1021/ja510549b
Type:
Article
ISSN:
00027863
Sponsors:
We thank one of the reviewers for suggesting us to model the pyrophosphatase system. Research reported in this publication was supported by the King Abdullah University of Science and Technology. We thank the HPC team of Enea (www.enea.it) for generous access to the ENEA-GRID and the HPC facilities CRESCO (www.cresco.enea.it) in Portici, Italy. A.P. thanks the Spanish MINECO for a Ramon y Cajal contract (RYC-2009-05226) and European Commission for a Career Integration Grant (CIG09-GA-2011-293900).
Appears in Collections:
Articles; Physical Sciences and Engineering (PSE) Division; Chemical Science Program; KAUST Catalysis Center (KCC)

Full metadata record

DC FieldValue Language
dc.contributor.authorChawla, Mohiten
dc.contributor.authorCredendino, Raffaeleen
dc.contributor.authorPoater, Alberten
dc.contributor.authorOliva, Romina M.en
dc.contributor.authorCavallo, Luigien
dc.date.accessioned2015-08-03T12:23:00Zen
dc.date.available2015-08-03T12:23:00Zen
dc.date.issued2015-01-14en
dc.identifier.issn00027863en
dc.identifier.doi10.1021/ja510549ben
dc.identifier.urihttp://hdl.handle.net/10754/564011en
dc.description.abstractUsing 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.en
dc.description.sponsorshipWe thank one of the reviewers for suggesting us to model the pyrophosphatase system. Research reported in this publication was supported by the King Abdullah University of Science and Technology. We thank the HPC team of Enea (www.enea.it) for generous access to the ENEA-GRID and the HPC facilities CRESCO (www.cresco.enea.it) in Portici, Italy. A.P. thanks the Spanish MINECO for a Ramon y Cajal contract (RYC-2009-05226) and European Commission for a Career Integration Grant (CIG09-GA-2011-293900).en
dc.publisherAmerican Chemical Society (ACS)en
dc.titleStructural stability, acidity, and halide selectivity of the fluoride riboswitch recognition siteen
dc.typeArticleen
dc.contributor.departmentKAUST Catalysis Center (KCC)en
dc.contributor.departmentPhysical Sciences and Engineering (PSE) Divisionen
dc.contributor.departmentChemical Science Programen
dc.identifier.journalJournal of the American Chemical Societyen
dc.contributor.institutionInstitut de Química Computacional i Catàlisi, Departament de Química, Universitat de GironaGirona, Spainen
dc.contributor.institutionDepartment of Sciences and Technologies, University Parthenope of Naples, Centro Direzionale Isola C4Naples, Italyen
kaust.authorCredendino, Raffaeleen
kaust.authorCavallo, Luigien
kaust.authorChawla, Mohiten
kaust.authorPoater, Alberten
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