Revisiting the structural flexibility of the complex p21ras-GTP: The catalytic conformation of the molecular switch II

Authors

  • T.A. Soares,

    1. Environmental Molecular Sciences Laboratory, Pacific Northwest National Laboratory, Richland, Washington
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  • J.H. Miller,

    1. Environmental Molecular Sciences Laboratory, Pacific Northwest National Laboratory, Richland, Washington
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  • T.P. Straatsma

    Corresponding author
    1. Environmental Molecular Sciences Laboratory, Pacific Northwest National Laboratory, Richland, Washington
    • Environmental Molecular Sciences Laboratory, Pacific Northwest National Laboratory, 902 Battelle Blvd., P.O. Box 999, Richland, WA 99352
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Abstract

The hydrolysis of GTP in p21ras triggers conformational changes that regulate the ras/ERK signaling pathway. An important active site residue is Gln61, which has been found to be mutated in 30% of human tumors. The dynamics of the active site conformation is studied by using molecular dynamics simulation of two independent structures of the GTP-bound uncomplexed enzyme. Two distinct conformations of the enzyme are observed, in which the side-chain residue Gln61 is in different orientations. Essential dynamics analysis is used to describe the essential motions in the transition between the two conformations. Results are compared with earlier simulations of p21ras and its complex with GTPase activating protein p21-GAP. Proteins 2001;45:297–312. © 2001 Wiley-Liss, Inc.

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