6QG4
Target information
- RCSB PDB
- 6QG4
- Title
- Structure of the mitogen activated kinase kinase 7 in complex with pyrazolopyrimidine inhibitor 1h
- Method
- X-RAY DIFFRACTION
- Resolution
- 2.3
- Classification
- TRANSFERASE
- Organism
- Homo sapiens
- Protein
- Dual specificity mitogen-activated protein kinase kinase 7 (O14733) Looking for covalent inhibitors of this target ?
- Year
- 2019
- Publication Title
- 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).
- 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.
- External Link
- RCSB PDB
Ligand information
- HET
- J0E
- Chain ID
- A
- HET Number
- 501
- Molecular Formula
- C19H20N6O2
- Structure
-
- IUPAC Name
- 1-[(3R)-3-[4-amino-3-(4-hydroxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]-1-piperidyl]prop-2-en-1-one
- InChI
- InChI=1S/C19H20N6O2/c1-2-15(27)24-9-3-4-13(10-24)25-19-16(18(20)21-11-22-19)17(23-25)12-5-7-14(26)8-6-12/h2,5-8,11,13,26H,1,3-4,9-10H2,(H2,20,21,22)/t13-/m1/s1
- InChI Key
- VRKPYFGIHAMROD-CYBMUJFWSA-N
- Canonical SMILES
- Oc1ccc(cc1)-c2nn(c(c23)ncnc3N)[C@@H]4CCCN(C4)C(=O)C=C
- Bioactivity data
- CI003845
Covalent Binding
- Warhead
- Michael Acceptor
- Reaction Mechanism
- Michael Addition
- Residue
- CYS : 218
- Residue Chain
- A
- Interactions
- Pharmacophore Model