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Literature DB >> 22225809

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

Fernando Martín-García¹, Jesús Ignacio Mendieta-Moreno, Eduardo López-Viñas, Paulino Gómez-Puertas, Jesús Mendieta.

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.

Entities: Chemical Mutation

Mesh：

Substances：

Year: 2012 PMID： 22225809 PMCID： PMC3250681 DOI： 10.1016/j.bpj.2011.11.4005

Source DB: PubMed Journal: Biophys J ISSN： 0006-3495 Impact factor: 4.033

23 in total

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