5FGW

Structure of Sda1 nuclease with bound zinc ion

Summary for 5FGW

• Entry DOI: 10.2210/pdb5fgw/pdb
• Related: 5FGU
• Descriptor: Extracellular streptodornase D, ZINC ION, CHLORIDE ION, ... (7 entities in total)
• Functional Keywords: beta-beta-alpha metal finger nuclease, sequence nonspecific dna binding, metal binding, dna binding protein
• Biological source: Streptococcus pyogenes
• Total number of polymer chains: 4
• Total formula weight: 119806.71

Authors

Moon, A.F.,Krahn, J.M.,Xun, L.,Cuneo, M.J.,Pedersen, L.C. (deposition date: 2015-12-21, release date: 2016-03-30, Last modification date: 2024-03-06)

Primary citation

Moon, A.F.,Krahn, J.M.,Lu, X.,Cuneo, M.J.,Pedersen, L.C.
Structural characterization of the virulence factor Sda1 nuclease from Streptococcus pyogenes.
Nucleic Acids Res., 44:3946-3957, 2016

PubMed Abstract: 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.

PubMed: 26969731
DOI: 10.1093/nar/gkw143

Experimental method

X-RAY DIFFRACTION (1.95 Å)