4QH0

Crystal structure of NucA from Streptococcus agalactiae with magnesium ion bound

4QH0 の概要

• エントリーDOI: 10.2210/pdb4qh0/pdb
• 関連するPDBエントリー: 4QGO
• 分子名称: DNA-entry nuclease (Competence-specific nuclease), MAGNESIUM ION, SULFATE ION, ... (6 entities in total)
• 機能のキーワード: nuclease, beta beta alpha metal finger, virulence factor, hydrolase
• 由来する生物種: Streptococcus agalactiae ILRI112
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 103601.95

構造登録者

Moon, A.F.,Gaudu, P.,Pedersen, L.C. (登録日: 2014-05-26, 公開日: 2014-11-19, 最終更新日: 2023-09-20)

主引用文献

Moon, A.F.,Gaudu, P.,Pedersen, L.C.
Structural characterization of the virulence factor nuclease A from Streptococcus agalactiae.
Acta Crystallogr.,Sect.D, 70:2937-2949, 2014

PubMed Abstract: The group B pathogen Streptococcus agalactiae commonly populates the human gut and urogenital tract, and is a major cause of infection-based mortality in neonatal infants and in elderly or immunocompromised adults. Nuclease A (GBS_NucA), a secreted DNA/RNA nuclease, serves as a virulence factor for S. agalactiae, facilitating bacterial evasion of the human innate immune response. GBS_NucA efficiently degrades the DNA matrix component of neutrophil extracellular traps (NETs), which attempt to kill and clear invading bacteria during the early stages of infection. In order to better understand the mechanisms of DNA substrate binding and catalysis of GBS_NucA, the high-resolution structure of a catalytically inactive mutant (H148G) was solved by X-ray crystallography. Several mutants on the surface of GBS_NucA which might influence DNA substrate binding and catalysis were generated and evaluated using an imidazole chemical rescue technique. While several of these mutants severely inhibited nuclease activity, two mutants (K146R and Q183A) exhibited significantly increased activity. These structural and biochemical studies have greatly increased our understanding of the mechanism of action of GBS_NucA in bacterial virulence and may serve as a foundation for the structure-based drug design of antibacterial compounds targeted to S. agalactiae.

PubMed: 25372684
DOI: 10.1107/S1399004714019725

実験手法

X-RAY DIFFRACTION (2 Å)