PDBsum entry 6qho

Transferase

PDB id: 6qho

Contents

Protein chain

275 a.a.

Ligands

J3H

Waters ×7

PDB id:

6qho

Name:

Transferase

Title:

Dual specificity mitogen-activated protein kinase kinase 7 in complex with pyrazolopyrimidine 1a

Structure:

Dual specificity mitogen-activated protein kinase kinase 7. Chain: a. Synonym: mapkk 7,jnk-activating kinase 2,mapk/erk kinase 7,mek 7, stress-activated protein kinase kinase 4,sapkk4,c-jun n-terminal kinase kinase 2,jnkk 2. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: map2k7, jnkk2, mek7, mkk7, prkmk7, skk4. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008

Resolution:

2.70Å R-factor: 0.226 R-free: 0.281

Authors:

P.Wolle,M.P.Mueller,D.Rauh

Key ref:

P.Wolle et al. (2019). 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). J Med Chem, 62, 5541-5546. PubMed id: 31083997 DOI: 10.1021/acs.jmedchem.9b00472

Date:

17-Jan-19 Release date: 22-May-19

Protein chain

O14733  (MP2K7_HUMAN) -  Dual specificity mitogen-activated protein kinase kinase 7 from Homo sapiens

Seq: 419 a.a.

Struc: 275 a.a.

Enzyme reactions

• Enzyme class: E.C.2.7.12.2 - mitogen-activated protein kinase kinase.
• Reaction:
  1. L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H⁺
  2. L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H⁺
  3. L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H⁺

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

DOI no: 10.1021/acs.jmedchem.9b00472

J Med Chem 62:5541-5546 (2019)

PubMed id: 31083997

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).

P.Wolle, J.Engel, S.Smith, L.Goebel, E.Hennes, J.Lategahn, D.Rauh.

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.