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The Role of Gln61 in HRas GTP hydrolysis: a quantum mechanics/molecular mechanics study.

ABSTRACT: Activation of the water molecule involved in GTP hydrolysis within the HRas·RasGAP system is analyzed using a tailored approach based on hybrid quantum mechanics/molecular mechanics (QM/MM) simulation. A new path emerges: transfer of a proton from the attacking water molecule to a second water molecule, then a different proton is transferred from this second water molecule to the GTP. Gln(61) will stabilize the transient OH(-) and H(3)O(+) molecules thus generated. This newly proposed mechanism was generated by using, for the first time to our knowledge, the entire HRas-RasGAP protein complex in a QM/MM simulation context. It also offers a rational explanation for previous experimental results regarding the decrease of GTPase rate found in the HRas Q61A mutant and the increase exhibited by the HRas Q61E mutant.

SUBMITTER: Martin-Garcia F

PROVIDER: S-EPMC3250681 | biostudies-literature | 2012 Jan

REPOSITORIES: biostudies-literature

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The Role of Gln61 in HRas GTP hydrolysis: a quantum mechanics/molecular mechanics study.

Martín-García Fernando F Mendieta-Moreno Jesús Ignacio JI López-Viñas Eduardo E Gómez-Puertas Paulino P Mendieta Jesús J Mendieta Jesús J

Biophysical journal 20120103 1

Activation of the water molecule involved in GTP hydrolysis within the HRas·RasGAP system is analyzed using a tailored approach based on hybrid quantum mechanics/molecular mechanics (QM/MM) simulation. A new path emerges: transfer of a proton from the attacking water molecule to a second water molecule, then a different proton is transferred from this second water molecule to the GTP. Gln(61) will stabilize the transient OH(-) and H(3)O(+) molecules thus generated. This newly proposed mechanism ...[more]

PMID: 22225809

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Dataset Information

The Role of Gln61 in HRas GTP hydrolysis: a quantum mechanics/molecular mechanics study.

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The Role of Gln61 in HRas GTP hydrolysis: a quantum mechanics/molecular mechanics study.

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