Invasive pneumococcal disease in HIV seropositive children and adolescents

Mattei, Sonia M.; Falleiros-Carvalho, Luiza Helena; Cavalcante, Nilton José Fernandes

doi:10.2223/jped.1762

Cited by 1 publication

(1 citation statement)

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“…IPD is one of the leading causes of opportunistic infections in young children, the elderly and in individuals immunocompromised due to cancer, diabetes or human immunodeficiency virus infection (3–6). Though favorable outcomes are primarily expected as a result of early detection and prompt antibacterial therapy, severe complications of IPD include bacteremia, meningitis and death (2,6,7,8). …”

Section: Introductionmentioning

confidence: 99%

Structural insights into catalytic and substrate binding mechanisms of the strategic EndA nuclease from Streptococcus pneumoniae

Moon¹,

Midon²,

Meiß³

et al. 2010

Nucleic Acids Research

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EndA is a sequence non-specific endonuclease that serves as a virulence factor during Streptococcus pneumoniae infection. Expression of EndA provides a strategy for evasion of the host's neutrophil extracellular traps, digesting the DNA scaffold structure and allowing further invasion by S. pneumoniae. To define mechanisms of catalysis and substrate binding, we solved the structure of EndA at 1.75 Å resolution. The EndA structure reveals a DRGH (Asp-Arg-Gly-His) motif-containing ββα-metal finger catalytic core augmented by an interesting ‘finger-loop’ interruption of the active site α-helix. Subsequently, we delineated DNA binding versus catalytic functionality using structure-based alanine substitution mutagenesis. Three mutants, H154A, Q186A and Q192A, exhibited decreased nuclease activity that appears to be independent of substrate binding. Glu205 was found to be crucial for catalysis, while residues Arg127/Lys128 and Arg209/Lys210 contribute to substrate binding. The results presented here provide the molecular foundation for development of specific antibiotic inhibitors for EndA.

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