2YA8
Crystal structure of Streptococcus pneumoniae NanA (TIGR4) in complex with Oseltamivir carboxylate
Summary for 2YA8
| Entry DOI | 10.2210/pdb2ya8/pdb |
| Descriptor | NEURAMINIDASE A, (3R,4R,5S)-4-(acetylamino)-5-amino-3-(pentan-3-yloxy)cyclohex-1-ene-1-carboxylic acid, CHLORIDE ION, ... (6 entities in total) |
| Functional Keywords | hydrolase, sialidase |
| Biological source | STREPTOCOCCUS PNEUMONIAE |
| Total number of polymer chains | 2 |
| Total formula weight | 111703.28 |
| Authors | Gut, H.,Xu, G.,Taylor, G.L.,Walsh, M.A. (deposition date: 2011-02-18, release date: 2011-04-27, Last modification date: 2024-05-08) |
| Primary citation | Gut, H.,Xu, G.,Taylor, G.L.,Walsh, M.A. Structural Basis for Streptococcus Pneumoniae Nana Inhibition by Influenza Antivirals Zanamivir and Oseltamivir Carboxylate. J.Mol.Biol., 409:496-, 2011 Cited by PubMed Abstract: 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. PubMed: 21514303DOI: 10.1016/J.JMB.2011.04.016 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.75 Å) |
Structure validation
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