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Determination and validation of mTOR kinase-domain 3D structure by homology modeling.

ABSTRACT: The AKT/mammalian target of rapamycin (mTOR) pathway is considered as one of the commonly activated and deregulated signaling pathways in human cancer. mTOR is associated with other proteins in two molecular complexes: mTOR complex 1/Raptor and the mTOR complex 2/Rictor. Using the crystal structure of the related lipid kinase PI3K?, we built a model of the catalytic region of mTOR. The modeling of the three-dimensional (3D) structure of the mTOR was performed by homology modeling program SWISS-MODEL. The quality and validation of the obtained model were performed using PROCHECK and PROVE softwares. The overall stereochemical property of the protein was assessed by the Ramachandran plot. The model validation was also done by docking of known inhibitors. In this paper, we describe and validate a 3D model for the mTOR catalytic site.

SUBMITTER: Lakhlili W

PROVIDER: S-EPMC4525790 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Determination and validation of mTOR kinase-domain 3D structure by homology modeling.

Lakhlili Wiame W Chevé Gwénaël G Yasri Abdelaziz A Ibrahimi Azeddine A

OncoTargets and therapy 20150730

The AKT/mammalian target of rapamycin (mTOR) pathway is considered as one of the commonly activated and deregulated signaling pathways in human cancer. mTOR is associated with other proteins in two molecular complexes: mTOR complex 1/Raptor and the mTOR complex 2/Rictor. Using the crystal structure of the related lipid kinase PI3Kγ, we built a model of the catalytic region of mTOR. The modeling of the three-dimensional (3D) structure of the mTOR was performed by homology modeling program SWISS-M ...[more]

PMID: 26257525

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