5xnw

Crystal structure of ExoY, a unique nucleotidyl cyclase toxin from Pseudomonas aeruginosa

spinqualitylabelsall models 5xnw, resolution 2.20Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5xnw is a 1 chain structure with sequence from Pseudomonas aeruginosa. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.201Å Ligands: GOL, SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function Q9I1S4_PSEAE Publication Abstract from PubMed BACKGROUND: The nucleotidyl cyclase toxin ExoY is an important virulence determinant of Pseudomonas aeruginosa that causes severe acute and chronic infections in immune-compromised individuals. Additionally, this unique T3SS effector shows a striking preference for cUMP, a newly identified non-canonical secondary messenger. Thereby, ExoY is also considered as a potential tool to study unexplored cUMP signaling pathways. METHODS: The crystal structure of ExoY was determined at 2.2A resolutions by in-situ proteolysis assisted crystallization and Rosetta-molecular replacement method. Additionally, isothermal calorimetric (ITC) and molecular dynamic (MD) simulation studies were also carried out to gain molecular insights into its substrate specificity and catalysis. RESULTS AND CONCLUSION: ExoY is a partially unfolded protein with higher propensity to form soluble higher-order oligomers. However, with meticulous attempts of removing of disordered regions by proteases, the recalcitrant ExoY could be successfully crystallized. The crystal structure of ExoY revealed similar overall structural fold present in other anthrax toxA family of nucleotidyl cyclases, with two-to-three distinctly conserved regions conferring specificity to eukaryotic binding partner. The in-vitro catalytic preference of ExoY is in the following order: cGMP > cUMP > cAMP > cCMP. The substrate specificity of ExoY mainly depends on its ability to bind NTP in proper geometrical orientations. ExoY also seems to prefer one-metal-ion dependent catalysis than two-metal-ion dependent catalysis. GENERAL SIGNIFICANCE: Our results provide much needed structural insight on ExoY, an important virulence determinant of Pseudomonas aeruginosa and an exciting tool to study non-canonical cNMP signaling pathways. ACCESSION NUMBERS: The structure factors and coordinate files have been deposited in the Protein Data Bank with accession number 5XNW. Crystal structure and substrate specificity of ExoY, a unique T3SS mediated secreted nucleotidyl cyclase toxin from Pseudomonas aeruginosa.,Khanppnavar B, Datta S Biochim Biophys Acta. 2018 May 30. pii: S0304-4165(18)30153-3. doi:, 10.1016/j.bbagen.2018.05.021. PMID:29859257 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also 3D Adenylyl cyclase 3D structures

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