English
 
User Manual Privacy Policy Disclaimer Contact us
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT

Released

Journal Article

Simulation of the solution structure of the H-ras p21-GTP complex

MPS-Authors
/persons/resource/persons95966

Wittinghofer,  Alfred
Emeritus Group Biophysics, Max Planck Institute for Medical Research, Max Planck Society;

/persons/resource/persons197463

Pai,  Emil F.
Emeritus Group Biophysics, Max Planck Institute for Medical Research, Max Planck Society;

Fulltext (public)
There are no public fulltexts stored in PuRe
Supplementary Material (public)
There is no public supplementary material available
Citation

Foley, C. K., Pedersen, L. G., Charifson, P. S., Darden, T. A., Wittinghofer, A., Pai, E. F., et al. (1992). Simulation of the solution structure of the H-ras p21-GTP complex. Biochemistry, 31(21), 4951-4959. doi:10.1021/bi00136a005.


Cite as: http://hdl.handle.net/11858/00-001M-0000-0019-AB5B-C
Abstract
An unconstrained simulation of the GTP-bound form of the H-ras protein p21 is performed in an aqueous environment with charge-neutralizing counterions. The simulation is compared to the 1.35-A structure of Pai et al. [(1990) EMBO J. 9, 2351] and a proposed alternate structure, in which the loop at residues 60-65 is modeled into a form which may activate a water molecule for the GTP hydrolysis. The simulation suggests that some protein intermolecular H-bond contacts which are present in the crystal structure are lost in the solvation process and this loss may lead to localized refolding of the molecule. For instance, we find that the gamma-phosphate of the GTP has somewhat weaker contact with the protein in the simulation structure. The antiparallel beta-sheet (residues 38-57) partially melts. The 60-65 loop, which is hypervariable in the X-ray study, is initially relatively distant from the gamma-phosphate region. However, this loop moves so as to sample the space around the gamma-phosphate. For a significant fraction of the simulation time, forms similar to the alternate structure are observed, and a water molecule is localized near the hydrolytic site. The molecular dynamics simulations of p21-GTP in solution support a postulated hydrolysis mechanism for the biological inactivation of the nucleotide complex based on crystallographic data.