ArticleProceedings of the National Academy of Sciences of the United States of America2006
Structural characterization of autoinhibited c-Met kinase produced by coexpression in bacteria with phosphatase.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 84 citations in OpenAlex.
- Molecular Basis of c‑MET Inhibition by Approved Small Molecule Drugs: A Structural Perspective.ACS medicinal chemistry letters · 2026Review
- Autoregulation of the MET receptor tyrosine kinase by its intracellular juxtamembrane domain.The Biochemical journal · 2025Article
- Tyrosine-Mediated Static and Dynamic Quenching of a Receptor Tyrosine Kinase Biosensor Reveals Inhibitor Binding Modes and Kinase Conformations.ACS chemical biology · 2025Article
- Article
- Conserved regulatory motifs in the juxtamembrane domain and kinase N-lobe revealed through deep mutational scanning of the MET receptor tyrosine kinase domain.bioRxiv : the preprint server for biology · 2024Article
- State of the structure address on MET receptor activation by HGF.Biochemical Society transactions · 2021Review
- Structural Basis for Targeting the Folded P-Loop Conformation of c-MET.ACS medicinal chemistry letters · 2021Article
- Structural versatility that serves the function of the HRD motif in the catalytic loop of protein tyrosine kinase, Src.Protein science : a publication of the Protein Society · 2019Article
- Structural Basis of TPR-Mediated Oligomerization and Activation of Oncogenic Fusion Kinases.Structure (London, England : 1993) · 2017Article
- Pharmacophore Mapping Approach for Drug Target Identification: A Chemical Synthesis and in Silico Study on Novel Thiadiazole Compounds.Journal of clinical and diagnostic research : JCDR · 2017Article
- Article
- The indole alkaloid meleagrin, from the olive tree endophytic fungus Penicillium chrysogenum, as a novel lead for the control of c-Met-dependent breast cancer proliferation, migration and invasion.Bioorganic & medicinal chemistry · 2016Article
- Development of Alkyne-Containing Pyrazolopyrimidines To Overcome Drug Resistance of Bcr-Abl Kinase.Journal of medicinal chemistry · 2015Article
- Spectrum of diverse genomic alterations define non-clear cell renal carcinoma subtypes.Nature genetics · 2015Article
- LY2801653 is an orally bioavailable multi-kinase inhibitor with potent activity against MET, MST1R, and other oncoproteins, and displays anti-tumor activities in mouse xenograft models.Investigational new drugs · 2013Article
- Biochemical and biophysical characterization of four EphB kinase domains reveals contrasting thermodynamic, kinetic and inhibition profiles.Bioscience reports · 2013Article
- The insulin receptor: both a prototypical and atypical receptor tyrosine kinase.Cold Spring Harbor perspectives in biology · 2013Review
- Assessing the range of kinase autoinhibition mechanisms in the insulin receptor family.The Biochemical journal · 2012Article
- Bioinformatics and variability in drug response: a protein structural perspective.Journal of the Royal Society, Interface · 2012Review
- Abl kinase constructs expressed in bacteria: facilitation of structural and functional studies including segmental labeling by expressed protein ligation.Molecular bioSystems · 2012Article
Corrections and comments
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Authors and funding
12 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Protein kinases are a large family of cell signaling mediators undergoing intensive research to identify inhibitors or modulators useful for medicine. As one strategy, small-molecule compounds that bind the active site with high affinity can be used to inhibit the enzyme activity. X-ray crystallography is a powerful method to reveal the structures of the kinase active sites, and thus aid in the design of high-affinity, selective inhibitors. However, a limitation still exists in the ability to produce purified kinases in amounts sufficient for crystallography. Furthermore, kinases exist in different conformation states as part of their normal regulation, and the ability to prepare crystals of kinases in these various states also remains a limitation. In this study, the c-Abl, c-Src, and c-Met kinases are produced in high yields in Escherichia coli by using a bicistronic vector encoding the PTP1B tyrosine phosphatase. A 100-fold lower dose of the inhibitor, Imatinib, was observed to inhibit the unphosphorylated form of c-Abl kinase prepared by using this vector, compared to the phosphorylated form produced without PTP1B, consistent with the known selectivity of this inhibitor for the unactivated conformation of the enzyme. Unphosphorylated c-Met kinase produced with this vector was used to obtain the crystal structure, at 2.15-A resolution, of the autoinhibited form of the kinase domain, revealing an intricate network of interactions involving c-Met residues documented previously to cause dysregulation when mutated in several cancers.
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