scholarly journals Conformational selection vs. induced fit: insights into the binding mechanisms of p38α MAP Kinase inhibitors

2020 ◽  
Vol 56 (62) ◽  
pp. 8818-8821
Author(s):  
Patrick Roser ◽  
Jörn Weisner ◽  
Juliane Stehle ◽  
Daniel Rauh ◽  
Malte Drescher
Keyword(s):  
Map Kinase ◽  
Direct Evidence ◽  
Kinase Inhibitors ◽  
Induced Fit ◽  
Conformational Selection ◽  
Ligand Type ◽  
Distance Restraints ◽  
Selection Mechanisms ◽  
P38α Map Kinase ◽  
Binding Mechanisms

Multilateration using EPR distance restraints shows direct evidence of both induced-fit and conformational selection mechanisms of p38α depending on the ligand type.

N-Phenyl-N-purin-6-yl ureas: The design and synthesis of p38α MAP kinase inhibitors

2003 ◽  
Vol 13 (6) ◽  
pp. 1191-1194 ◽  
Author(s):  
Zehong Wan ◽  
Jeffrey C. Boehm ◽  
Michael J. Bower ◽  
Shouki Kassis ◽  
John C. Lee ◽  
...  
Keyword(s):  
Map Kinase ◽  
Kinase Inhibitors ◽  
Design And Synthesis ◽  
P38α Map Kinase

Design of Potent and Selective 2-Aminobenzimidazole-Based p38α MAP Kinase Inhibitors with Excellent in Vivo Efficacy

2005 ◽  
Vol 48 (7) ◽  
pp. 2270-2273 ◽  
Author(s):  
Alfonso de Dios ◽  
Chuan Shih ◽  
Beatriz López de Uralde ◽  
Concepción Sánchez ◽  
Miriam del Prado ◽  
...  
Keyword(s):  
Map Kinase ◽  
Kinase Inhibitors ◽  
In Vivo Efficacy ◽  
P38α Map Kinase

Dibenzepinones, dibenzoxepines and benzosuberones based p38α MAP kinase inhibitors: Their pharmacophore modelling, 3D-QSAR and docking studies

2019 ◽  
Vol 110 ◽  
pp. 175-185 ◽  
Author(s):  
Mohemmed Faraz Khan ◽  
Garima Verma ◽  
Perwez Alam ◽  
Mymoona Akhter ◽  
Md Afroz Bakht ◽  
...  
Keyword(s):  
Map Kinase ◽  
Kinase Inhibitors ◽  
3D Qsar ◽  
Docking Studies ◽  
Pharmacophore Modelling ◽  
P38α Map Kinase

scholarly journals Conformational propensities of intrinsically disordered proteins influence the mechanism of binding and folding

2015 ◽  
Vol 112 (31) ◽  
pp. 9614-9619 ◽  
Author(s):  
Munehito Arai ◽  
Kenji Sugase ◽  
H. Jane Dyson ◽  
Peter E. Wright
Keyword(s):  
Intrinsically Disordered Proteins ◽  
Terminal Region ◽  
Relaxation Dispersion ◽  
Disordered Proteins ◽  
Conformational Ensemble ◽  
Induced Fit ◽  
Conformational Selection ◽  
Intrinsically Disordered ◽  
Factor C ◽  
Binding Mechanisms

Intrinsically disordered proteins (IDPs) frequently function in protein interaction networks that regulate crucial cellular signaling pathways. Many IDPs undergo transitions from disordered conformational ensembles to folded structures upon binding to their cellular targets. Several possible binding mechanisms for coupled folding and binding have been identified: folding of the IDP after association with the target (“induced fit”), or binding of a prefolded state in the conformational ensemble of the IDP to the target protein (“conformational selection”), or some combination of these two extremes. The interaction of the intrinsically disordered phosphorylated kinase-inducible domain (pKID) of the cAMP-response element binding (CREB) protein with the KIX domain of a general transcriptional coactivator CREB-binding protein (CBP) provides an example of the induced-fit mechanism. Here we show by NMR relaxation dispersion experiments that a different intrinsically disordered ligand, the transactivation domain of the transcription factor c-Myb, interacts with KIX at the same site as pKID but via a different binding mechanism that involves elements of conformational selection and induced fit. In contrast to pKID, the c-Myb activation domain has a strong propensity for spontaneous helix formation in its N-terminal region, which binds to KIX in a predominantly folded conformation. The C-terminal region of c-Myb exhibits a much smaller helical propensity and likely folds via an induced-fit process after binding to KIX. We propose that the intrinsic secondary structure propensities of pKID and c-Myb determine their binding mechanisms, consistent with their functions as inducible and constitutive transcriptional activators.

Thermal Denaturation:  A Method to Rank Slow Binding, High-Affinity P38α MAP Kinase Inhibitors

2003 ◽  
Vol 46 (22) ◽  
pp. 4669-4675 ◽  
Author(s):  
Rachel R. Kroe ◽  
John Regan ◽  
Al Proto ◽  
Gregory W. Peet ◽  
Tapon Roy ◽  
...  
Keyword(s):  
Map Kinase ◽  
Thermal Denaturation ◽  
Kinase Inhibitors ◽  
High Affinity ◽  
P38α Map Kinase

scholarly journals An optimized and versatile synthesis to pyridinylimidazole-type p38α mitogen activated protein kinase inhibitors

2015 ◽  
Vol 13 (43) ◽  
pp. 10699-10704 ◽  
Author(s):  
Ahmed El-Gokha ◽  
Stefan A. Laufer ◽  
Pierre Koch
Keyword(s):  
Protein Kinase ◽  
Map Kinase ◽  
Kinase Inhibitors ◽  
Protein Kinase Inhibitors ◽  
Mitogen Activated Protein Kinase ◽  
Synthetic Approach ◽  
Mitogen Activated Protein ◽  
P38α Map Kinase

An optimized and diverse synthetic approach for the preparation of potent pyridinylimidazole-based p38α MAP kinase inhibitors is reported.

Identification of p38α MAP kinase inhibitors by pharmacophore based virtual screening

2014 ◽  
Vol 49 ◽  
pp. 18-24 ◽  
Author(s):  
Rahul P. Gangwal ◽  
Nihar R. Das ◽  
Kaushik Thanki ◽  
Mangesh V. Damre ◽  
Gaurao V. Dhoke ◽  
...  
Keyword(s):  
Virtual Screening ◽  
Map Kinase ◽  
Kinase Inhibitors ◽  
P38α Map Kinase
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