TI  - The  <prot>Ras</prot> - <prot>RasGAP</prot>  complex: structural basis for GTPase activation and its
      loss in oncogenic <prot>Ras</prot> mutants.
PG  - 333-8
AB  - The three-dimensional structure of the complex between human  <prot>H-Ras</prot>  bound
      to guanosine diphosphate and the guanosine triphosphatase
      (GTPase)-activating domain of the human <prot>GTPase-activating protein</prot>  <prot>p120GAP</prot> 
      (<prot>GAP-334</prot>) in the presence of aluminum fluoride was solved at a resolution
      of 2.5 angstroms. The structure shows the partly hydrophilic and partly
      hydrophobic nature of the communication between the two molecules, which
      explains the sensitivity of the interaction toward both salts and lipids.
      An arginine side chain (arginine-789) of <prot>GAP-334</prot> is supplied into the
      active site of <prot>Ras</prot> to neutralize developing charges in the transition
      state. The switch II region of  <prot>Ras</prot>  is stabilized by  <prot>GAP-334</prot> , thus allowing
      glutamine-61 of <prot>Ras</prot>, mutation of which activates the oncogenic potential,
      to participate in catalysis. The structural arrangement in the active site
      is consistent with a mostly associative mechanism of phosphoryl transfer
      and provides an explanation for the activation of <prot>Ras</prot> by glycine-12 and
      glutamine-61 mutations. Glycine-12 in the transition state mimic is within
      van der Waals distance of both arginine-789 of <prot>GAP-334</prot> and glutamine-61 of
      <prot>Ras</prot>, and even its mutation to alanine would disturb the arrangements of
      residues in the transition state.
AD  - Max-Planck-Institut fur molekulare Physiologie, Abteilung Strukturelle
