6vve

Legionella pneumophila Lpg2603 kinase bound to IP6, Mn2+, and ADP

spinqualitylabelsall models 6vve, resolution 1.85Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6vve is a 1 chain structure with sequence from Legionella pneumophila. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.85Å Ligands: ADP, IHP, MN, MSE Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function Q5ZSB6_LEGPH Publication Abstract from PubMed The transfer of a phosphate from ATP to a protein substrate, a modification known as protein phosphorylation, is catalyzed by protein kinases. Protein kinases play a crucial role in virtually every cellular activity. Recent studies of atypical protein kinases have highlighted the structural similarity of the kinase superfamily despite notable differences in primary amino acid sequence. Here, using a bioinformatics screen, we searched for putative protein kinases in the intracellular bacterial pathogen Legionella pneumophila and identified the type 4 secretion system (T4SS) effector Lpg2603 as a remote member of the protein kinase superfamily. Employing an array of biochemical and structural biology approaches, including in vitro kinase assays and isothermal calorimetry, we show that Lpg2603 is an active protein kinase with several atypical structural features. Importantly, we found that the eukaryote-specific host signaling molecule inositol hexakisphosphate (IP6) is required for Lpg2603 kinase activity. Crystal structures of Lpg2603 in the apo-form and when bound to IP6 revealed an active-site rearrangement that allows for ATP binding and catalysis. Our results on the structure and activity of Lpg2603 reveal a unique mode of regulation of a protein kinase, provide the first example of a bacterial kinase that requires IP6 for its activation, and may aid future work on the function of this effector during Legionella pathogenesis. A Legionella effector kinase is activated by host inositol hexakisphosphate.,Sreelatha A, Nolan C, Park BC, Pawlowski K, Tomchick DR, Tagliabracci VS J Biol Chem. 2020 Mar 30. pii: RA120.013067. doi: 10.1074/jbc.RA120.013067. PMID:32229585 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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