A phosphoryl transfer intermediate in the GTPase reaction of Ras in complex with its GTPase-activating protein

Proc Natl Acad Sci U S A. 2006 Sep 19;103(38):13911-6. doi: 10.1073/pnas.0604128103. Epub 2006 Sep 12.

Abstract

The hydrolysis of nucleoside triphosphates by enzymes is used as a regulation mechanism in key biological processes. Here, the GTP hydrolysis of the protein complex of Ras with its GTPase-activating protein is monitored at atomic resolution in a noncrystalline state by time-resolved FTIR spectroscopy. At 900 ms, after the attack of water at the gamma-phosphate, there appears a H2PO4- intermediate that is shown to be hydrogen-bonded in an eclipsed conformation to the beta-phosphate of GDP. The H2PO4- intermediate is in a position where it can either reform GTP or be released from the protein in 7 s in the rate-limiting step of the GTPase reaction. We propose that such an intermediate also occurs in other GTPases and ATPases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Enzyme Activation
  • Guanosine Triphosphate / chemistry
  • Guanosine Triphosphate / metabolism
  • Hydrogen Bonding
  • Models, Molecular
  • Molecular Structure
  • Phosphates / chemistry
  • Phosphates / metabolism
  • Protein Conformation*
  • Protons
  • Spectroscopy, Fourier Transform Infrared
  • ras GTPase-Activating Proteins / chemistry*
  • ras GTPase-Activating Proteins / metabolism
  • ras Proteins / chemistry*
  • ras Proteins / metabolism

Substances

  • Phosphates
  • Protons
  • ras GTPase-Activating Proteins
  • Guanosine Triphosphate
  • ras Proteins