3CIO

The kinase domain of Escherichia coli tyrosine kinase ETK

Summary for 3CIO

• Entry DOI: 10.2210/pdb3cio/pdb
• Descriptor: Tyrosine-protein kinase etk, CHLORIDE ION (3 entities in total)
• Functional Keywords: etk, wzc, escherichia coli tyrosine kinase domain, signaling protein, transferase, inner membrane, membrane, phosphoprotein, transmembrane, tyrosine-protein kinase
• Biological source: Escherichia coli
• Cellular location: Cell inner membrane; Multi-pass membrane protein: P38134
• Total number of polymer chains: 2
• Total formula weight: 66843.63

Authors

Lee, D.C.,Zheng, J.,Jia, Z. (deposition date: 2008-03-11, release date: 2008-06-03, Last modification date: 2024-02-21)

Primary citation

Lee, D.C.,Zheng, J.,She, Y.M.,Jia, Z.
Structure of Escherichia coli tyrosine kinase Etk reveals a novel activation mechanism.
Embo J., 27:1758-1766, 2008

PubMed Abstract: While protein tyrosine (Tyr) kinases (PTKs) have been extensively characterized in eukaryotes, far less is known about their emerging counterparts in prokaryotes. The inner-membrane Wzc/Etk protein belongs to the bacterial PTK family, which has an important function in regulating the polymerization and transport of virulence-determining capsular polysaccharide (CPS). The kinase uses a unique two-step activation process involving intra-phosphorylation of a Tyr residue, although the molecular mechanism remains unknown. Herein, we report the first crystal structure of a bacterial PTK, the C-terminal kinase domain of Escherichia coli Tyr kinase (Etk) at 2.5-A resolution. The fold of the Etk kinase domain differs markedly from that of eukaryotic PTKs. Based on the observed structure and supporting mass spectrometric evidence of Etk, a unique activation mechanism is proposed that involves the phosphorylated Tyr residue, Y574, at the active site and its specific interaction with a previously unidentified key Arg residue, R614, to unblock the active site. Both in vitro kinase activity and in vivo antibiotics resistance studies using structure-guided mutants further support the novel activation mechanism.

PubMed: 18497741
DOI: 10.1038/emboj.2008.97

Experimental method

X-RAY DIFFRACTION (2.5 Å)