PDBsum entry 4joa

Transferase/transferase inhibitor

PDB id: 4joa

Contents

Protein chain

251 a.a.

Ligands

3DK

Waters ×26

PDB id:

4joa

Name:

Transferase/transferase inhibitor

Title:

Crystal structure of human anaplastic lymphoma kinase in complex with 7-azaindole based inhibitor

Structure:

Alk tyrosine kinase receptor. Chain: a. Fragment: catalytic domain, unp residues 1072-1410. Synonym: anaplastic lymphoma kinase. Engineered: yes. Mutation: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: alk. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108.

Resolution:

2.70Å R-factor: 0.253 R-free: 0.290

Authors:

S.Hosahalli,N.R.Krishnamurthy,A.Lakshminarasimhan

Key ref:

V.R.Gummadi et al. (2013). Discovery of 7-azaindole based anaplastic lymphoma kinase (ALK) inhibitors: wild type and mutant (L1196M) active compounds with unique binding mode. Bioorg Med Chem Lett, 23, 4911-4918. PubMed id: 23880539 DOI: 10.1016/j.bmcl.2013.06.071

Date:

18-Mar-13 Release date: 17-Jul-13

Protein chain

Q9UM73  (ALK_HUMAN) -  ALK tyrosine kinase receptor from Homo sapiens

Seq: 1620 a.a.

Struc: 251 a.a.

Enzyme reactions

• Enzyme class: E.C.2.7.10.1 - receptor 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.2013.06.071

Bioorg Med Chem Lett 23:4911-4918 (2013)

PubMed id: 23880539

Discovery of 7-azaindole based anaplastic lymphoma kinase (ALK) inhibitors: wild type and mutant (L1196M) active compounds with unique binding mode.

V.R.Gummadi, S.Rajagopalan, C.Y.Looi, M.Paydar, G.A.Renukappa, B.R.Ainan, N.R.Krishnamurthy, S.K.Panigrahi, K.Mahasweta, S.Raghuramachandran, M.Rajappa, A.Ramanathan, A.Lakshminarasimhan, M.Ramachandra, P.F.Wong, M.R.Mustafa, S.Nanduri, S.Hosahalli.

ABSTRACT

We have identified a novel 7-azaindole series of anaplastic lymphoma kinase (ALK) inhibitors. Compounds 7b, 7 m and 7 n demonstrate excellent potencies in biochemical and cellular assays. X-ray crystal structure of one of the compounds (7 k) revealed a unique binding mode with the benzyl group occupying the back pocket, explaining its potency towards ALK and selectivity over tested kinases particularly Aurora-A. This binding mode is in contrast to that of known ALK inhibitors such as Crizotinib and NVP-TAE684 which occupy the ribose binding pocket, close to DFG motif.