4rt0 | pdb_00004rt0

Structure of the Alg44 PilZ domain from Pseudomonas aeruginosa PAO1 in complex with c-di-GMP

spinqualitylabelsall models 4rt0, resolution 1.80Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4rt0 is a 3 chain structure with sequence from Pseudomonas aeruginosa PAO1. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: C2E, EDO, MSE Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function ALG44_PSEAE Required for alginate biosynthesis. Publication Abstract from PubMed Pseudomonas aeruginosa is an opportunistic human pathogen that secretes the exopolysaccharide alginate during infection of the respiratory tract of individuals afflicted with cystic fibrosis and chronic obstructive pulmonary disease. Among the proteins required for alginate production, Alg44 has been identified as an inner membrane protein whose bis-(3',5')-cyclic dimeric guanosine monophosphate (c-di-GMP) binding activity post-translationally regulates alginate secretion. In this study, we report the 1.8 A crystal structure of the cytoplasmic region of Alg44 in complex with dimeric self-intercalated c-di-GMP and characterize its dinucleotide-binding site using mutational analysis. The structure shows that the c-di-GMP binding region of Alg44 adopts a PilZ domain fold with a dimerization mode not previously observed for this family of proteins. Calorimetric binding analysis of residues in the c-di-GMP binding site demonstrate that mutation of Arg-17 and Arg-95 alters the binding stoichiometry between c-di-GMP and Alg44 from 2:1 to 1:1. Introduction of these mutant alleles on the P. aeruginosa chromosome show that the residues required for binding of dimeric c-di-GMP in vitro are also required for efficient alginate production in vivo. These results suggest that the dimeric form of c-di-GMP represents the biologically active signaling molecule needed for the secretion of an important virulence factor produced by P. aeruginosa. Dimeric c-di-GMP Is Required for Post-translational Regulation of Alginate Production in Pseudomonas aeruginosa.,Whitney JC, Whitfield GB, Marmont LS, Yip P, Neculai AM, Lobsanov YD, Robinson H, Ohman DE, Howell PL J Biol Chem. 2015 May 15;290(20):12451-62. doi: 10.1074/jbc.M115.645051. Epub, 2015 Mar 27. PMID:25817996 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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