5fgw

Structure of Sda1 nuclease with bound zinc ion

spinqualitylabelsall models 5fgw, resolution 1.95Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5fgw is a 4 chain structure with sequence from "micrococcus_scarlatinae"_klein_1884 "micrococcus scarlatinae" klein 1884. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: ACT, CL, EDO, NA, ZN Related: 5fgu Gene: sda1, sdaD2, HKU360_01468, SD90_06600 ("Micrococcus scarlatinae" Klein 1884) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Infection by Group A Streptococcus pyogenes (GAS) is a leading cause of severe invasive disease in humans, including streptococcal toxic shock syndrome and necrotizing fasciitis. GAS infections lead to nearly 163,000 annual deaths worldwide. Hypervirulent strains of S. pyogenes have evolved a plethora of virulence factors that aid in disease-by promoting bacterial adhesion to host cells, subsequent invasion of deeper tissues and blocking the immune system's attempts to eradicate the infection. Expression and secretion of the extracellular nuclease Sda1 is advantageous for promoting bacterial dissemination throughout the host organism, and evasion of the host's innate immune response. Here we present two crystal structures of Sda1, as well as biochemical studies to address key structural features and surface residues involved in DNA binding and catalysis. In the active site, Asn211 is observed to directly chelate a hydrated divalent metal ion and Arg124, on the putative substrate binding loop, likely stabilizes the transition state during phosphodiester bond cleavage. These structures provide a foundation for rational drug design of small molecule inhibitors to be used in prevention of invasive streptococcal disease. Structural characterization of the virulence factor Sda1 nuclease from Streptococcus pyogenes.,Moon AF, Krahn JM, Lu X, Cuneo MJ, Pedersen LC Nucleic Acids Res. 2016 May 5;44(8):3946-57. doi: 10.1093/nar/gkw143. Epub 2016, Mar 11. PMID:26969731 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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