ArticleThe Biochemical journal2015
Crystal structure of an SH2-kinase construct of c-Abl and effect of the SH2 domain on kinase activity.
Article in The Biochemical journal, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 34 citations in OpenAlex.
- Non-receptor tyrosine kinase signaling pathways and therapeutic implications.Signal transduction and targeted therapy · 2026Review
- eRMSF: A Python Package for Ensemble-Based RMSF Analysis of Biomolecular Systems.Journal of chemical information and modeling · 2025Article
- Prospective Evaluation of Structure-Based Simulations Reveal Their Ability to Predict the Impact of Kinase Mutations on Inhibitor Binding.The journal of physical chemistry. B · 2025Article
- Prospective evaluation of structure-based simulations reveal their ability to predict the impact of kinase mutations on inhibitor binding.bioRxiv : the preprint server for biology · 2025Article
- Dual modality feature fused neural network integrating binding site information for drug target affinity prediction.NPJ digital medicine · 2025Article
- Non-Receptor Tyrosine Kinases: Their Structure and Mechanistic Role in Tumor Progression and Resistance.Cancers · 2024Review
- An interaction-based drug discovery screen explains known SARS-CoV-2 inhibitors and predicts new compound scaffolds.Scientific reports · 2023Article
- Allosteric regulation of autoinhibition and activation of c-Abl.Computational and structural biotechnology journal · 2022Article
- Molecular dynamics simulations of the conformational plasticity in the active pocket of salt-inducible kinase 2 (SIK2) multi-state binding with bosutinib.Computational and structural biotechnology journal · 2022Article
- Dasatinib-SIK2 Binding Elucidated by Homology Modeling, Molecular Docking, and Dynamics Simulations.ACS omega · 2021Article
- Conformational states dynamically populated by a kinase determine its function.Science (New York, N.Y.) · 2020Article
- Btk SH2-kinase interface is critical for allosteric kinase activation and its targeting inhibits B-cell neoplasms.Nature communications · 2020Article
- The Src module: an ancient scaffold in the evolution of cytoplasmic tyrosine kinases.Critical reviews in biochemistry and molecular biology · 2018Review
- Predicting resistance of clinical Abl mutations to targeted kinase inhibitors using alchemical free-energy calculations.Communications biology · 2018Article
- Structural and functional dissection of the DH and PH domains of oncogenic Bcr-Abl tyrosine kinase.Nature communications · 2017Article
- Atomic view of the energy landscape in the allosteric regulation of Abl kinase.Nature structural & molecular biology · 2017Article
- Multifunctional Abl kinases in health and disease.Journal of cell science · 2016Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Constitutive activation of the non-receptor tyrosine kinase c-Abl (cellular Abelson tyrosine protein kinase 1, Abl1) in the Bcr (breakpoint cluster region)-Abl1 fusion oncoprotein is the molecular cause of chronic myeloid leukaemia (CML). Recent studies have indicated that an interaction between the SH2 (Src-homology 2) domain and the N-lobe (N-terminal lobe) of the c-Abl kinase domain (KD) has a critical role in leukaemogenesis [Grebien et al. (2011) Cell 147, 306-319; Sherbenou et al. (2010) Blood 116, 3278-3285]. To dissect the structural basis of this phenomenon, we studied c-Abl constructs comprising the SH2 and KDs in vitro. We present a crystal structure of an SH2-KD construct bound to dasatinib, which contains the relevant interface between the SH2 domain and the N-lobe of the KD. We show that the presence of the SH2 domain enhances kinase activity moderately and that this effect depends on contacts in the SH2/N-lobe interface and is abrogated by specific mutations. Consistently, formation of the interface decreases slightly the association rate of imatinib with the KD. That the effects are small compared with the dramatic in vivo consequences suggests an important function of the SH2-N-lobe interaction might be to help disassemble the auto-inhibited conformation of c-Abl and promote processive phosphorylation, rather than substantially stimulate kinase activity.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.