3sxr
From Proteopedia
Crystal structure of BMX non-receptor tyrosine kinase complex with dasatinib
Structural highlights
Function[BMX_HUMAN] Non-receptor tyrosine kinase that plays central but diverse modulatory roles in various signaling processes involved in the regulation of actin reorganization, cell migration, cell proliferation and survival, cell adhesion, and apoptosis. Participates in signal transduction stimulated by growth factor receptors, cytokine receptors, G-protein coupled receptors, antigen receptors and integrins. Induces tyrosine phosphorylation of BCAR1 in response to integrin regulation. Activation of BMX by integrins is mediated by PTK2/FAK1, a key mediator of integrin signaling events leading to the regulation of actin cytoskeleton and cell motility. Plays a critical role in TNF-induced angiogenesis, and implicated in the signaling of TEK and FLT1 receptors, 2 important receptor families essential for angiogenesis. Required for the phosphorylation and activation of STAT3, a transcription factor involved in cell differentiation. Also involved in interleukin-6 (IL6) induced differentiation. Plays also a role in programming adaptive cytoprotection against extracellular stress in different cell systems, salivary epithelial cells, brain endothelial cells, and dermal fibroblasts. May be involved in regulation of endocytosis through its interaction with an endosomal protein RUFY1. May also play a role in the growth and differentiation of hematopoietic cells; as well as in signal transduction in endocardial and arterial endothelial cells.[1] [2] [3] [4] [5] [6] [7] Publication Abstract from PubMedBone marrow kinase in the X chromosome (BMX), 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 (BTK) and IL-2-inducible T cell kinase (ITK) are known, the crystal structures of other Tec family kinases have remained elusive. We report the X-ray crystal structures of BMX in complex with dasatinib at 2.4A resolution and PP2 at 1.9A resolution. The BMX 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 BMX in the ATP binding pocket and display similar binding modes to that observed in other Tec and Src protein kinases. The BMX structures identify conformational elements of the DFG-motif that could potentially be utilized to design potent and/or selective BMX inhibitors. X-Ray Crystal Structure of Bone Marrow Kinase in the X Chromosome; a Tec Family Kinase.,Muckelbauer J, Sack JS, Ahmed N, Burke J, Chang CY, Gao M, Tino J, Xie D, Tebben AJ Chem Biol Drug Des. 2011 Aug 30. doi: 10.1111/j.1747-0285.2011.01230.x. PMID:21883956[8] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
| ||||||||||||||||||||||||
