X-ray crystal structure of bone marrow kinase in the x chromosome: a Tec family kinase.

Published

Journal Article

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.

Full Text

Cited Authors

  • Muckelbauer, J; Sack, JS; Ahmed, N; Burke, J; Chang, CY; Gao, M; Tino, J; Xie, D; Tebben, AJ

Published Date

  • November 2011

Published In

Volume / Issue

  • 78 / 5

Start / End Page

  • 739 - 748

PubMed ID

  • 21883956

Pubmed Central ID

  • 21883956

Electronic International Standard Serial Number (EISSN)

  • 1747-0285

International Standard Serial Number (ISSN)

  • 1747-0277

Digital Object Identifier (DOI)

  • 10.1111/j.1747-0285.2011.01230.x

Language

  • eng