2xcy

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. 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, PDBe, RCSB, PDBsum, ProSAT Function [SIA_ASPFU] Sialidase is able to release sialic acid from a wide variety of natural substrates including bovine salivary mucin, colominic acid, bovine fetuin, a serum glycoprotein containing both alpha-2-6 and alpha-2-3-linkages in a ratio of about 3:2, and glycoproteins and glycolipids from thermally denatured human lung epithelial cells. Does not show any trans-sialidase activity since it is able to remove terminal sialic acid residues but is unable to catalyze their transfer to the acceptor substrate. 2-keto-3-deoxynononic acid (KDN) is the preferred substrate and A.fumigatus can utilize KDN as a sole carbon source. 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 3D structures

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