2xzj

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2xzj, resolution 1.84Å ()
Ligands: , ,
Activity: Exo-alpha-sialidase, with EC number 3.2.1.18
Related: 2xcy, 2xzi, 2xzk


Resources: FirstGlance, OCA, PDBsum, RCSB
Coordinates: save as pdb, mmCIF, xml



Contents

THE ASPERGILLUS FUMIGATUS SIALIDASE IS A KDNASE: STRUCTURAL AND MECHANISTIC INSIGHTS

Publication Abstract from PubMed

Aspergillus fumigatus is a filamentous fungus that can cause severe respiratory disease in immunocompromised individuals. A putative sialidase from A. fumigatus was recently cloned and shown to be relatively poor in cleaving N-acetylneuraminic acid (Neu5Ac) in comparison to bacterial sialidases. Here we present the first crystal structure of a fungal sialidase. When the apo structure was compared to bacterial sialidase structures, the active site of the Aspergillus enzyme suggested that Neu5Ac would be a poor substrate due to a smaller pocket that normally accommodates the acetamido group of Neu5Ac in sialidases. A sialic acid with a hydroxyl in place of an acetamido group is 2-keto-3-deoxynononic acid (KDN). We show that KDN is the preferred substrate for the A. fumigatus sialidase and that A. fumigatus can utilise KDN as a sole carbon source. A 1.4Angstrom resolution crystal structure of the enzyme in complex with KDN reveals KDN in the active site in a boat conformation, and nearby a second binding site occupied by KDN in a chair conformation, suggesting that polyKDN may be a natural substrate. The enzyme is not inhibited by the sialidase transition state analogue 2-deoxy-2,3-dehydro-N-acetylneuraminic acid (Neu5Ac2en) but is inhibited by the related KDN2en that we show bound to the enzyme in a 1.84Angstrom resolution crystal structure. Using a fluorinated KDN substrate, we present a 1.5Angstrom resolution structure of a covalently bound catalytic intermediate. The A. fumigatus sialidase is therefore a KDNase with a similar catalytic mechanism to Neu5Ac exosialidases, and this study represents the first structure of a KDNase.

The Aspergillus fumigatus sialidase is a KDNase: structural and mechanistic insights., Telford JC, Yeung JH, Xu G, Kiefel MJ, Watts AG, Hader S, Chan J, Bennet AJ, Moore MM, Taylor GL, J Biol Chem. 2011 Jan 19. PMID:21247893

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

About this Structure

2xzj is a 2 chain structure with sequence from Aspergillus fumigatus. Full crystallographic information is available from OCA.

See Also

Reference

  • Telford JC, Yeung JH, Xu G, Kiefel MJ, Watts AG, Hader S, Chan J, Bennet AJ, Moore MM, Taylor GL. The Aspergillus fumigatus sialidase is a KDNase: structural and mechanistic insights. J Biol Chem. 2011 Jan 19. PMID:21247893 doi:10.1074/jbc.M110.207043

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