2ya7

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Crystal structure of Streptococcus pneumoniae NanA (TIGR4) in complex with ZanamivirCrystal structure of Streptococcus pneumoniae NanA (TIGR4) in complex with Zanamivir

Structural highlights

2ya7 is a 4 chain structure with sequence from Streptococcus pneumoniae TIGR4. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 1.89Å
Ligands:,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

NANA_STREE

Publication Abstract from PubMed

The human pathogen Streptococcus pneumoniae is the major cause of bacterial meningitis, respiratory tract infection, septicemia, and otitis media. The bacterium expresses neuraminidase (NA) proteins that contribute to pathogenesis by cleaving sialic acids from host glycoconjugates, thereby enhancing biofilm formation and colonization. Recent in vivo experiments have shown that antiviral compounds, widely used in clinics and designed to inhibit influenza NA, significantly reduce biofilm formation and nasopharyngeal colonization of S. pneumoniae in mice. Here, we present the structural basis for the beneficial effect of these compounds against pneumococcal infection. Crystal structures of pneumococcal NanA in complex with zanamivir and oseltamivir carboxylate are discussed, correlated with measured inhibitory constants K(i), and compared with the binding modes of the inhibitors in the viral enzyme. Inhibitor structures show for the first time how clinically approved anti-influenza compounds interact with an NA of the human pathogen S. pneumoniae and give a rational explanation for their antibacterial effects.

Structural Basis for Streptococcus pneumoniae NanA Inhibition by Influenza Antivirals Zanamivir and Oseltamivir Carboxylate.,Gut H, Xu G, Taylor GL, Walsh MA J Mol Biol. 2011 Jun 17;409(4):496-503. Epub 2011 Apr 14. PMID:21514303[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

See Also

References

  1. Gut H, Xu G, Taylor GL, Walsh MA. Structural Basis for Streptococcus pneumoniae NanA Inhibition by Influenza Antivirals Zanamivir and Oseltamivir Carboxylate. J Mol Biol. 2011 Jun 17;409(4):496-503. Epub 2011 Apr 14. PMID:21514303 doi:10.1016/j.jmb.2011.04.016

2ya7, resolution 1.89Å

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OCA