5d6t

Crystal Structure of Aspergillus clavatus Sph3 in complex with GalNAc

spinqualitylabelsall models 5d6t, resolution 1.93Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5d6t is a 1 chain structure with sequence from Aspergillus clavatus NRRL 1. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: CL, NGA, SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function A1CJQ5_ASPCL Publication Abstract from PubMed Aspergillus fumigatus is the most virulent species within the Aspergillus genus and causes invasive infections with high mortality rates. The exopolysaccharide galactosaminogalactan (GAG) contributes to the virulence of A. fumigatus. A co-regulated five-gene cluster has been identified and proposed to encode the proteins required for GAG biosynthesis. One of these genes, sph3, is predicted to encode a protein belonging to the spherulin 4 family, a protein family with no known function. Construction of an sph3-deficient mutant demonstrated that the gene is necessary for GAG production. To determine the role of Sph3 in GAG biosynthesis, we determined the structure of Aspergillus clavatus Sph3 to 1.25 A. The structure revealed a (beta/alpha)8 fold, with similarities to glycoside hydrolase families 18, 27, and 84. Recombinant Sph3 displayed hydrolytic activity against both purified and cell wall-associated GAG. Structural and sequence alignments identified three conserved acidic residues, Asp-166, Glu-167, and Glu-222, that are located within the putative active site groove. In vitro and in vivo mutagenesis analysis demonstrated that all three residues are important for activity. Variants of Asp-166 yielded the greatest decrease in activity suggesting a role in catalysis. This work shows that Sph3 is a glycoside hydrolase essential for GAG production and defines a new glycoside hydrolase family, GH135. Sph3 Is a Glycoside Hydrolase Required for the Biosynthesis of Galactosaminogalactan in Aspergillus fumigatus.,Bamford NC, Snarr BD, Gravelat FN, Little DJ, Lee MJ, Zacharias CA, Chabot JC, Geller AM, Baptista SD, Baker P, Robinson H, Howell PL, Sheppard DC J Biol Chem. 2015 Nov 13;290(46):27438-50. doi: 10.1074/jbc.M115.679050. Epub, 2015 Sep 4. PMID:26342082 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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