6QG7
Target information
- RCSB PDB
- 6QG7
- Title
- Structure of the mitogen activated kinase kinase 7 in complex with pyrazolopyrimidine 1k
- Method
- X-RAY DIFFRACTION
- Resolution
- 2.1
- 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
- 6HL
- Chain ID
- A
- HET Number
- 501
- Molecular Formula
- C23H22N6O
- Structure
-
- IUPAC Name
- 1-[(3R)-3-[4-amino-3-(1-naphthyl)pyrazolo[3,4-d]pyrimidin-1-yl]-1-piperidyl]prop-2-en-1-one
- InChI
- InChI=1S/C23H22N6O/c1-2-19(30)28-12-6-9-16(13-28)29-23-20(22(24)25-14-26-23)21(27-29)18-11-5-8-15-7-3-4-10-17(15)18/h2-5,7-8,10-11,14,16H,1,6,9,12-13H2,(H2,24,25,26)/t16-/m1/s1
- InChI Key
- WAJKANXMXJLTKT-MRXNPFEDSA-N
- Canonical SMILES
- C=CC(=O)N1CCC[C@H](C1)n(c(c23)ncnc3N)nc2-c4cccc(c45)cccc5
- Bioactivity data
- CI004068
Covalent Binding
- Warhead
- Michael Acceptor
- Reaction Mechanism
- Michael Addition
- Residue
- CYS : 218
- Residue Chain
- A
- Interactions
- Pharmacophore Model