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Publication Abstract from PubMed

The surface-exposed beta-galactosidase BgaC from Streptococcus pneumoniae was reported to be a virulence factor because of its specific hydrolysis activity towards the beta(1,3)-linked galactose and N-acetylglucosamine [Galbeta(1,3)NAG] moiety of oligosaccharides on the host molecules. Here we report the crystal structure of BgaC at 1.8 and its complex with galactose at 1.95 . At pH 5.5 to 8.0, BgaC exists as a stable homodimer, each subunit of which consists of three distinct domains: a catalytic domain of a classic (beta/alpha)8 TIM barrel, followed by two all-beta domains (ABDs) of unknown function. The side-walls of the TIM beta-barrel and a loop extended from the first ABD constitute the active site. Superposition of the galactose-complexed structure to the apo-form revealed significant conformational changes of residues Trp243 and Tyr455. Simulation of a putative substrate entrance tunnel and modeling of a complex structure with Galbeta(1,3)NAG enabled us to assign three key residues to the specific catalysis. Site-directed mutagenesis in combination with activity assays further proved that residues Trp240 and Tyr455 contribute to stabilizing the N-acetylglucosamine moiety, whereas Trp243 is critical for fixing the galactose ring. Moreover, we propose that BgaC and other galactosidases in the GH-35 family share a common domain organization and a conserved substrate-determinant aromatic residue protruding from the second domain.

Structural insights into the substrate specificity of Streptococcus pneumoniae beta(1,3) galactosidase BgaC.,Cheng W, Wang L, Jiang YL, Bai XH, Chu J, Li Q, Yu G, Liang QL, Zhou CZ, Chen Y J Biol Chem. 2012 May 16. PMID:22593580^[1]

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