Next Article in Journal
Flavonoids as Important Molecules of Plant Interactions with the Environment
Next Article in Special Issue
Identification and Characterization of Amlexanox as a G Protein-Coupled Receptor Kinase 5 Inhibitor
Previous Article in Journal
Radical Addition to Iminium Ions and Cationic Heterocycles
Previous Article in Special Issue
Design and Synthesis of Thiazolo[5,4-f]quinazolines as DYRK1A Inhibitors, Part I
Open AccessArticle

Structural Elucidation of the DFG-Asp in and DFG-Asp out States of TAM Kinases and Insight into the Selectivity of Their Inhibitors

1
OriBase Pharma, Parc Euromedecine, Cap Gamma, 1682, rue de la Valsière, 34189 Montpellier, France
2
Laboratoire de Chimie des Plantes et de Synthèse Organique et Bioorganique, URAC23, Université Mohammed V, Faculté des Sciences B.P., 1014 Rabat, Morocco
*
Author to whom correspondence should be addressed.
Molecules 2014, 19(10), 16223-16239; https://doi.org/10.3390/molecules191016223
Received: 31 July 2014 / Revised: 24 September 2014 / Accepted: 26 September 2014 / Published: 10 October 2014
(This article belongs to the Special Issue Design and Study of Kinase Inhibitors)
Structural elucidation of the active (DFG-Asp in) and inactive (DFG-Asp out) states of the TAM family of receptor tyrosine kinases is required for future development of TAM inhibitors as drugs. Herein we report a computational study on each of the three TAM members Tyro-3, Axl and Mer. DFG-Asp in and DFG-Asp out homology models of each one were built based on the X-ray structure of c-Met kinase, an enzyme with a closely related sequence. Structural validation and in silico screening enabled identification of critical amino acids for ligand binding within the active site of each DFG-Asp in and DFG-Asp out model. The position and nature of amino acids that differ among Tyro-3, Axl and Mer, and the potential role of these residues in the design of selective TAM ligands, are discussed. View Full-Text
Keywords: tyrosine kinase; TAM kinase family; homology model; kinase selectivity tyrosine kinase; TAM kinase family; homology model; kinase selectivity
Show Figures

Graphical abstract

MDPI and ACS Style

Messoussi, A.; Peyronnet, L.; Feneyrolles, C.; Chevé, G.; Bougrin, K.; Yasri, A. Structural Elucidation of the DFG-Asp in and DFG-Asp out States of TAM Kinases and Insight into the Selectivity of Their Inhibitors. Molecules 2014, 19, 16223-16239. https://doi.org/10.3390/molecules191016223

AMA Style

Messoussi A, Peyronnet L, Feneyrolles C, Chevé G, Bougrin K, Yasri A. Structural Elucidation of the DFG-Asp in and DFG-Asp out States of TAM Kinases and Insight into the Selectivity of Their Inhibitors. Molecules. 2014; 19(10):16223-16239. https://doi.org/10.3390/molecules191016223

Chicago/Turabian Style

Messoussi, Abdellah; Peyronnet, Lucile; Feneyrolles, Clémence; Chevé, Gwénaël; Bougrin, Khalid; Yasri, Aziz. 2014. "Structural Elucidation of the DFG-Asp in and DFG-Asp out States of TAM Kinases and Insight into the Selectivity of Their Inhibitors" Molecules 19, no. 10: 16223-16239. https://doi.org/10.3390/molecules191016223

Find Other Styles

Article Access Map by Country/Region

1
Only visits after 24 November 2015 are recorded.
Search more from Scilit
 
Search
Back to TopTop