Characterization of Covalent Pyrazolopyrimidine-MKK7 Complexes and a Report on a Unique DFG-in/Leu-in Conformation of Mitogen-Activated Protein Kinase Kinase 7 (MKK7).

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2019
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Abstract
Pyrazolopyrimidines are well-established as covalent inhibitors of protein kinases such as the epidermal growth factor receptor or Bruton's tyrosine kinase, and we recently described their potential in targeting mitogen-activated protein kinase kinase 7 (MKK7). Herein, we report the structure-activity relationship of pyrazolopyrimidine-based MKK7 inhibitors and solved several complex crystal structures to gain insights into their binding mode. In addition, we present two structures of apo-MKK7, exhibiting a DFG-out and an unprecedented DFG-in/Leu-in conformation.
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wolle2019characterizationjournal Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Wolle, Patrik;Engel, Julian;Smith, Steven;Goebel, Lisa;Hennes, Elisabeth;Lategahn, Jonas;Rauh, Daniel;
Journal Journal of medicinal chemistry
Year 2019
DOI
10.1021/acs.jmedchem.9b00472
URL
Keywords
VEGFR-2 phthalimide drug-likeness dna gyrase b antimicrobial and anticancer activities molecular modeling study

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