3SXR

Crystal structure of BMX non-receptor tyrosine kinase complex with dasatinib

Summary for 3SXR

• Entry DOI: 10.2210/pdb3sxr/pdb
• Related: 3SXS
• Descriptor: Cytoplasmic tyrosine-protein kinase BMX, N-(2-CHLORO-6-METHYLPHENYL)-2-({6-[4-(2-HYDROXYETHYL)PIPERAZIN-1-YL]-2-METHYLPYRIMIDIN-4-YL}AMINO)-1,3-THIAZOLE-5-CARBOXAMIDE, SULFATE ION, ... (4 entities in total)
• Functional Keywords: transferase-transferase inhibitor complex, transferase/transferase inhibitor
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm: P51813
• Total number of polymer chains: 2
• Total formula weight: 63684.26

Authors

Sack, J.,Muckelbauer, J. (deposition date: 2011-07-15, release date: 2011-09-21, Last modification date: 2024-02-28)

Primary citation

Muckelbauer, J.,Sack, J.S.,Ahmed, N.,Burke, J.,Chang, C.Y.,Gao, M.,Tino, J.,Xie, D.,Tebben, A.J.
X-ray crystal structure of bone marrow kinase in the x chromosome: a Tec family kinase.
Chem.Biol.Drug Des., 78:739-748, 2011

PubMed Abstract: Bone marrow kinase in the X chromosome, a member of the Tec family of tyrosine kinases, plays a role in both monocyte/macrophage trafficking as well as cytokine secretion. Although the structures of Tec family kinases Bruton's tyrosine kinase and IL-2-inducible T-cell kinase are known, the crystal structures of other Tec family kinases have remained elusive. We report the X-ray crystal structures of bone marrow kinase in the X chromosome in complex with dasatinib at 2.4 Å resolution and PP2 at 1.9 Å resolution. The bone marrow kinase in the X chromosome structures reveal a typical kinase protein fold; with well-ordered protein conformation that includes an open/extended activation loop and a stabilized DFG-motif rendering the kinase in an inactive conformation. Dasatinib and PP2 bind to bone marrow kinase in the X chromosome in the ATP binding pocket and display similar binding modes to that observed in other Tec and Src protein kinases. The bone marrow kinase in the X chromosome structures identify conformational elements of the DFG-motif that could potentially be utilized to design potent and/or selective bone marrow kinase in the X chromosome inhibitors.

PubMed: 21883956
DOI: 10.1111/j.1747-0285.2011.01230.x

Experimental method

X-RAY DIFFRACTION (2.4 Å)