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

Mohit Chawla; Raffaele Credendino; Albert Poater; Romina M. Oliva; Luigi Cavallo

doi:10.1021/ja510549b

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

Mohit Chawla, Raffaele Credendino, Albert Poater, Romina M. Oliva, Luigi Cavallo

Research output: Contribution to journal › Article › peer-review

27 Scopus citations

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.

Original language	English (US)
Pages (from-to)	299-306
Number of pages	8
Journal	Journal of the American Chemical Society
Volume	137
Issue number	1
DOIs	https://doi.org/10.1021/ja510549b
State	Published - Dec 23 2014

Bibliographical note

KAUST Repository Item: Exported on 2020-10-01
Acknowledgements: 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).

ASJC Scopus subject areas

Biochemistry
Colloid and Surface Chemistry
General Chemistry
Catalysis

Access to Document

10.1021/ja510549b

Cite this

@article{2d9e4e4db9114a4fb0afb6ff325c132d,

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

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.",

author = "Mohit Chawla and Raffaele Credendino and Albert Poater and Oliva, {Romina M.} and Luigi Cavallo",

note = "KAUST Repository Item: Exported on 2020-10-01 Acknowledgements: 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).",

year = "2014",

month = dec,

day = "23",

doi = "10.1021/ja510549b",

language = "English (US)",

volume = "137",

pages = "299--306",

journal = "Journal of the American Chemical Society",

issn = "0002-7863",

publisher = "American Chemical Society",

number = "1",

}

TY - JOUR

T1 - Structural stability, acidity, and halide selectivity of the fluoride riboswitch recognition site

AU - Chawla, Mohit

AU - Credendino, Raffaele

AU - Poater, Albert

AU - Oliva, Romina M.

AU - Cavallo, Luigi

N1 - KAUST Repository Item: Exported on 2020-10-01 Acknowledgements: 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).

PY - 2014/12/23

Y1 - 2014/12/23

N2 - 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.

AB - 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.

UR - http://hdl.handle.net/10754/564011

UR - https://pubs.acs.org/doi/10.1021/ja510549b

UR - http://www.scopus.com/inward/record.url?scp=84921059060&partnerID=8YFLogxK

U2 - 10.1021/ja510549b

DO - 10.1021/ja510549b

M3 - Article

C2 - 25487435

SN - 0002-7863

VL - 137

SP - 299

EP - 306

JO - Journal of the American Chemical Society

JF - Journal of the American Chemical Society

IS - 1

ER -

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

Abstract

Bibliographical note

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this