Neutron Crystal Structure of RAS GTPase Puts in Question the Protonation State of the GTP γ-Phosphate

Ryan Knihtila; Genevieve Holzapfel; Kevin Weiss; Flora Meilleur; Carla Mattos

doi:10.1074/jbc.M115.679860

Neutron Crystal Structure of RAS GTPase Puts in Question the Protonation State of the GTP γ-Phosphate

Ryan Knihtila, Genevieve Holzapfel, Kevin Weiss, Flora Meilleur, Carla Mattos

Biological Labeling and Scattering

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39 Scopus citations

Abstract

Background: The GTP nucleotide is thought to be fully deprotonated when bound to RAS. Results: The neutron crystal structure of RAS bound to the GTP analogue GppNHp shows a protonated γ-phosphate. Conclusion: The active site of RAS significantly increases the pKa of the nucleotide. Significance: This work provides insight to the GTP hydrolysis mechanism, with implications to the superfamily of small GTPases.

Original language	English
Pages (from-to)	31025-31036
Number of pages	12
Journal	Journal of Biological Chemistry
Volume	290
Issue number	52
DOIs	https://doi.org/10.1074/jbc.M115.679860
State	Published - Dec 25 2015

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title = "Neutron Crystal Structure of RAS GTPase Puts in Question the Protonation State of the GTP γ-Phosphate",

abstract = "Background: The GTP nucleotide is thought to be fully deprotonated when bound to RAS. Results: The neutron crystal structure of RAS bound to the GTP analogue GppNHp shows a protonated γ-phosphate. Conclusion: The active site of RAS significantly increases the pKa of the nucleotide. Significance: This work provides insight to the GTP hydrolysis mechanism, with implications to the superfamily of small GTPases.",

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AU - Knihtila, Ryan

AU - Holzapfel, Genevieve

AU - Weiss, Kevin

AU - Meilleur, Flora

AU - Mattos, Carla

PY - 2015/12/25

Y1 - 2015/12/25

N2 - Background: The GTP nucleotide is thought to be fully deprotonated when bound to RAS. Results: The neutron crystal structure of RAS bound to the GTP analogue GppNHp shows a protonated γ-phosphate. Conclusion: The active site of RAS significantly increases the pKa of the nucleotide. Significance: This work provides insight to the GTP hydrolysis mechanism, with implications to the superfamily of small GTPases.

AB - Background: The GTP nucleotide is thought to be fully deprotonated when bound to RAS. Results: The neutron crystal structure of RAS bound to the GTP analogue GppNHp shows a protonated γ-phosphate. Conclusion: The active site of RAS significantly increases the pKa of the nucleotide. Significance: This work provides insight to the GTP hydrolysis mechanism, with implications to the superfamily of small GTPases.

UR - https://www.scopus.com/pages/publications/84951810234

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DO - 10.1074/jbc.M115.679860

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VL - 290

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EP - 31036

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

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Neutron Crystal Structure of RAS GTPase Puts in Question the Protonation State of the GTP γ-Phosphate

Abstract

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