PDBsum entry 4x7j

Transferase/transferase inhibitor

PDB id: 4x7j

Contents

Protein chain

257 a.a.

Ligands

3Z1

TLA

Waters ×106

PDB id:

4x7j

Name:

Transferase/transferase inhibitor

Title:

Co-crystal structure of perk with 2-amino-n-[4-methoxy-3- (trifluoromethyl)phenyl]-4-methyl-3-[2-(methylamino)quinazolin-6- yl]benzamide inhibitor

Structure:

Eukaryotic translation initiation factor 2-alpha kinase 3, eukaryotic translation initiation factor 2-alpha kinase 3. Chain: a. Synonym: prkr-like endoplasmic reticulum kinase,pancreatic eif2-alpha kinase,hspek. Engineered: yes. Mutation: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: eif2ak3, pek, perk. Expressed in: escherichia coli. Expression_system_taxid: 562

Resolution:

2.30Å R-factor: 0.196 R-free: 0.225

Authors:

P.L.Shaffer,A.M.Long,H.Chen

Key ref:

A.L.Smith et al. (2015). Discovery of 1H-pyrazol-3(2H)-ones as potent and selective inhibitors of protein kinase R-like endoplasmic reticulum kinase (PERK). J Med Chem, 58, 1426-1441. PubMed id: 25587754 DOI: 10.1021/jm5017494

Date:

09-Dec-14 Release date: 28-Jan-15

Protein chain

Q9NZJ5  (E2AK3_HUMAN) -  Eukaryotic translation initiation factor 2-alpha kinase 3 from Homo sapiens

Seq: 1116 a.a.

Struc: 257 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

Enzyme reactions

• Enzyme class: E.C.2.7.11.1 - non-specific serine/threonine protein 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⁺

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

reference

DOI no: 10.1021/jm5017494

J Med Chem 58:1426-1441 (2015)

PubMed id: 25587754

Discovery of 1H-pyrazol-3(2H)-ones as potent and selective inhibitors of protein kinase R-like endoplasmic reticulum kinase (PERK).

A.L.Smith, K.L.Andrews, H.Beckmann, S.F.Bellon, P.J.Beltran, S.Booker, H.Chen, Y.A.Chung, N.D.D'Angelo, J.Dao, K.R.Dellamaggiore, P.Jaeckel, R.Kendall, K.Labitzke, A.M.Long, S.Materna-Reichelt, P.Mitchell, M.H.Norman, D.Powers, M.Rose, P.L.Shaffer, M.M.Wu, J.R.Lipford.

ABSTRACT

The structure-based design and optimization of a novel series of selective PERK inhibitors are described resulting in the identification of 44 as a potent, highly selective, and orally active tool compound suitable for PERK pathway biology exploration both in vitro and in vivo.