2xcy | pdb_00002xcy

CRYSTAL STRUCTURE OF ASPERGILLUS FUMIGATUS SIALIDASE

spinqualitylabelsall models 2xcy, resolution 1.84Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2xcy is a 2 chain structure with sequence from Aspergillus fumigatus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: CL, GOL NonStd Res: MSE Activity: Exo-alpha-sialidase, with EC number 3.2.1.18 Resources: FirstGlance, OCA, RCSB, PDBsum Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. 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. See Also Neuraminidase

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