PDBsum entry 4zim

Transferase/transferase inhibitor

PDB id: 4zim

Contents

Protein chains

287 a.a.

Ligands

4OK ×2

Waters ×262

PDB id:

4zim

Name:

Transferase/transferase inhibitor

Title:

Crystal structure of janus kinase 2 in complex with a 9h-carbazole-1- carboxamide inhibitor

Structure:

Tyrosine-protein kinase jak2. Chain: a, b. Fragment: catalytic domain, unp residues 839-1132. Synonym: janus kinase 2,jak-2. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: jak2. Expressed in: escherichia coli. Expression_system_taxid: 562

Resolution:

2.65Å R-factor: 0.204 R-free: 0.274

Authors:

J.S.Sack

Key ref:

K.Zimmermann et al. (2015). 9H-Carbazole-1-carboxamides as potent and selective JAK2 inhibitors. Bioorg Med Chem Lett, 25, 2809-2812. PubMed id: 25987372 DOI: 10.1016/j.bmcl.2015.04.101

Date:

28-Apr-15 Release date: 03-Jun-15

Protein chains

O60674  (JAK2_HUMAN) -  Tyrosine-protein kinase JAK2 from Homo sapiens

Seq: 1132 a.a.

Struc: 287 a.a.

Enzyme reactions

• Enzyme class: E.C.2.7.10.2 - non-specific protein-tyrosine kinase.
• Reaction: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H⁺

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

Added reference

DOI no: 10.1016/j.bmcl.2015.04.101

Bioorg Med Chem Lett 25:2809-2812 (2015)

PubMed id: 25987372

9H-Carbazole-1-carboxamides as potent and selective JAK2 inhibitors.

K.Zimmermann, X.Sang, H.A.Mastalerz, W.L.Johnson, G.Zhang, Q.Liu, D.Batt, L.J.Lombardo, D.Vyas, G.L.Trainor, J.S.Tokarski, M.V.Lorenzi, D.You, M.M.Gottardis, J.Lippy, J.Khan, J.S.Sack, A.V.Purandare.

ABSTRACT

The discovery, synthesis, and characterization of 9H-carbazole-1-carboxamides as potent and selective ATP-competitive inhibitors of Janus kinase 2 (JAK2) are discussed. Optimization for JAK family selectivity led to compounds 14 and 21, with greater than 45-fold selectivity for JAK2 over all other members of the JAK kinase family.