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

T. A. Soares; J. H. Miller; T. P. Straatsma

doi:10.1002/prot.1150

Revisiting the structural flexibility of the complex p21^ras- GTP: The catalytic conformation of the molecular switch II

T. A. Soares, J. H. Miller, T. P. Straatsma

Research output: Contribution to journal › Article › peer-review

14 Scopus citations

Abstract

The hydrolysis of GTP in p21^ras 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 p21^ras and its complex with GTPase activating protein p21-GAP.

Original language	English
Pages (from-to)	297-312
Number of pages	16
Journal	Proteins: Structure, Function and Genetics
Volume	45
Issue number	4
DOIs	https://doi.org/10.1002/prot.1150
State	Published - Dec 1 2001
Externally published	Yes

Keywords

Catalytic mechanism
Essential dynamics
Molecular dynamics
Molecular switches
Nonlinear poisson-boltzmann signal transduction

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10.1002/prot.1150

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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.",

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AU - Miller, J. H.

AU - Straatsma, T. P.

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AB - 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.

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Revisiting the structural flexibility of the complex p21^ras- GTP: The catalytic conformation of the molecular switch II

Abstract

Keywords

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