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

Lakhlili W, Chevé G, Yasri A, Ibrahimi A - Onco Targets Ther (2015)

Bottom Line: The quality and validation of the obtained model were performed using PROCHECK and PROVE softwares.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.

View Article: PubMed Central - PubMed

Affiliation: Laboratoire de Biotechnologie (MedBiotech), Faculté de Médecine et de Pharmacie de Rabat, Université Mohammed V de Rabat, Rabat, Morroco.

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 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-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.

No MeSH data available.


Related in: MedlinePlus

Constructed 3D model of mTOR catalytic domain.Notes: The model is oriented with the N-lobe at the top and the hinge is colored in orange. The C-lobe is at the bottom of the figure, the substrate binding loop is in purple and the activation loop in red. The rest of the binding site is represented by the alpha helix C, gatekeeper (ILE-2096), and the residue Lys2046 which is involved in catalysis and the DFG motif on sticks.Abbreviations: mTOR, mammalian target of rapamycin; 3D, three-dimensional.
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f3-ott-8-1923: Constructed 3D model of mTOR catalytic domain.Notes: The model is oriented with the N-lobe at the top and the hinge is colored in orange. The C-lobe is at the bottom of the figure, the substrate binding loop is in purple and the activation loop in red. The rest of the binding site is represented by the alpha helix C, gatekeeper (ILE-2096), and the residue Lys2046 which is involved in catalysis and the DFG motif on sticks.Abbreviations: mTOR, mammalian target of rapamycin; 3D, three-dimensional.

Mentions: The 3D structure prediction (Figure 3) was carried out by alignment of target sequences with template structures (retrieved from PDB database 3L13), using a Swiss Model Server.13Figure 4 shows the constructed model and the superposed model with template.


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

Lakhlili W, Chevé G, Yasri A, Ibrahimi A - Onco Targets Ther (2015)

Constructed 3D model of mTOR catalytic domain.Notes: The model is oriented with the N-lobe at the top and the hinge is colored in orange. The C-lobe is at the bottom of the figure, the substrate binding loop is in purple and the activation loop in red. The rest of the binding site is represented by the alpha helix C, gatekeeper (ILE-2096), and the residue Lys2046 which is involved in catalysis and the DFG motif on sticks.Abbreviations: mTOR, mammalian target of rapamycin; 3D, three-dimensional.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4525790&req=5

f3-ott-8-1923: Constructed 3D model of mTOR catalytic domain.Notes: The model is oriented with the N-lobe at the top and the hinge is colored in orange. The C-lobe is at the bottom of the figure, the substrate binding loop is in purple and the activation loop in red. The rest of the binding site is represented by the alpha helix C, gatekeeper (ILE-2096), and the residue Lys2046 which is involved in catalysis and the DFG motif on sticks.Abbreviations: mTOR, mammalian target of rapamycin; 3D, three-dimensional.
Mentions: The 3D structure prediction (Figure 3) was carried out by alignment of target sequences with template structures (retrieved from PDB database 3L13), using a Swiss Model Server.13Figure 4 shows the constructed model and the superposed model with template.

Bottom Line: The quality and validation of the obtained model were performed using PROCHECK and PROVE softwares.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.

View Article: PubMed Central - PubMed

Affiliation: Laboratoire de Biotechnologie (MedBiotech), Faculté de Médecine et de Pharmacie de Rabat, Université Mohammed V de Rabat, Rabat, Morroco.

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 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-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.

No MeSH data available.


Related in: MedlinePlus