PDBsum entry 4xli

Transferase/transferase inhibitor

PDB id: 4xli

Contents

Protein chains

264 a.a.

Ligands

1N1 ×2

Metals

_ZN

Waters ×32

PDB id:

4xli

Name:

Transferase/transferase inhibitor

Title:

Crystal structure of abl2/arg kinase in complex with dasatinib

Structure:

Non-specific protein-tyrosine kinase. Chain: a, b. Engineered: yes

Source:

Mus musculus. Mouse. Organism_taxid: 10090. Gene: abl2. Expressed in: trichoplusia ni. Expression_system_taxid: 7111.

Resolution:

2.50Å R-factor: 0.157 R-free: 0.205

Authors:

B.H.Ha,T.J.Boggon

Key ref:

B.H.Ha et al. (2015). Structure of the ABL2/ARG kinase in complex with dasatinib. Acta Crystallogr F Struct Biol Commun, 71, 443-448. PubMed id: 25849507 DOI: 10.1107/S2053230X15004793

Date:

13-Jan-15 Release date: 01-Apr-15

Protein chains

Q4JIM5  (ABL2_MOUSE) -  Tyrosine-protein kinase ABL2 from Mus musculus

Seq: 1182 a.a.

Struc: 264 a.a.*

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

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: 10.1107/S2053230X15004793

Acta Crystallogr F Struct Biol Commun 71:443-448 (2015)

PubMed id: 25849507

Structure of the ABL2/ARG kinase in complex with dasatinib.

B.H.Ha, M.A.Simpson, A.J.Koleske, T.J.Boggon.

ABSTRACT

ABL2/ARG (ABL-related gene) belongs to the ABL (Abelson tyrosine-protein kinase) family of tyrosine kinases. ARG plays important roles in cell morphogenesis, motility, growth and survival, and many of these biological roles overlap with the cellular functions of the ABL kinase. Chronic myeloid leukemia (CML) is associated with constitutive ABL kinase activation resulting from fusion between parts of the breakpoint cluster region (BCR) and ABL1 genes. Similarly, fusion of the ETV6 (Tel) and ARG genes drives some forms of T-cell acute lymphoblastic leukemia (T-ALL) and acute myeloid leukemia (AML). Dasatinib is a tyrosine kinase inhibitor used for the treatment of CML by inhibiting ABL, and while it also inhibits ARG, there is currently no structure of ARG in complex with dasatinib. Here, the co-crystal structure of the mouse ARG catalytic domain with dasatinib at 2.5 Å resolution is reported. Dasatinib-bound ARG is found in the DFG-in conformation although it is nonphosphorylated on the activation-loop tyrosine. In this structure the glycine-rich P-loop is found in a relatively open conformation compared with other known ABL family-inhibitor complex structures.