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1b9s

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1b9s, resolution 2.50Å ()
Ligands: , ,
Activity: Exo-alpha-sialidase, with EC number 3.2.1.18
Resources: FirstGlance, OCA, PDBsum, RCSB
Coordinates: save as pdb, mmCIF, xml



Contents

NOVEL AROMATIC INHIBITORS OF INFLUENZA VIRUS NEURAMINIDASE MAKE SELECTIVE INTERACTIONS WITH CONSERVED RESIDUES AND WATER MOLECULES IN THE ACTIVE SITE

Publication Abstract from PubMed

The active site of type A or B influenza virus neuraminidase is composed of 11 conserved residues that directly interact with the substrate, sialic acid. An aromatic benzene ring has been used to replace the pyranose of sialic acid in our design of novel neuraminidase inhibitors. A bis(hydroxymethyl)pyrrolidinone ring was constructed in place of the N-acetyl group on the sialic acid. The hydroxymethyl groups replace two active site water molecules, which resulted in the high affinity of the nanomolar inhibitors. However, these inhibitors have greater potency for type A influenza virus than for type B influenza virus. To resolve the differences, we determined the X-ray crystal structure of three benzoic acid substituted inhibitors bound to the active site of B/Lee/40 neuraminidase. The investigation of a hydrophobic aliphatic group and a hydrophilic guanidino group on the aromatic inhibitors shows changes in the interaction with the active site residue Glu275. The results provide an explanation for the difference in efficacy of these inhibitors against types A and B viruses, even though the 11 active site residues of the neuraminidase are conserved.

Novel aromatic inhibitors of influenza virus neuraminidase make selective interactions with conserved residues and water molecules in the active site., Finley JB, Atigadda VR, Duarte F, Zhao JJ, Brouillette WJ, Air GM, Luo M, J Mol Biol. 1999 Nov 12;293(5):1107-19. PMID:10547289

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

About this Structure

1b9s is a 1 chain structure with sequence from Viruses. Full crystallographic information is available from OCA.

See Also

Reference

  • Finley JB, Atigadda VR, Duarte F, Zhao JJ, Brouillette WJ, Air GM, Luo M. Novel aromatic inhibitors of influenza virus neuraminidase make selective interactions with conserved residues and water molecules in the active site. J Mol Biol. 1999 Nov 12;293(5):1107-19. PMID:10547289 doi:10.1006/jmbi.1999.3180

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