4E8D

Crystal structure of streptococcal beta-galactosidase

Summary for 4E8D

• Entry DOI: 10.2210/pdb4e8d/pdb
• Related: 4E8C
• Descriptor: Glycosyl hydrolase, family 35, GLYCEROL (3 entities in total)
• Functional Keywords: tim barrel, beta-propeller, glycohydrolase, hydrolase
• Biological source: Streptococcus pneumoniae
• Total number of polymer chains: 2
• Total formula weight: 139237.11

Authors

Cheng, W.,Wang, L.,Bai, X.H.,Jiang, Y.L.,Li, Q.,Yu, G.,Zhou, C.Z.,Chen, Y.X. (deposition date: 2012-03-20, release date: 2012-05-30, Last modification date: 2023-11-08)

Primary citation

Cheng, W.,Wang, L.,Jiang, Y.L.,Bai, X.H.,Chu, J.,Li, Q.,Yu, G.,Liang, Q.L.,Zhou, C.Z.,Chen, Y.X.
Structural insights into the substrate specificity of Streptococcus pneumoniae beta (1,3)-galactosidase BgaC
J.Biol.Chem., 287:22910-22918, 2012

PubMed Abstract: The surface-exposed β-galactosidase BgaC from Streptococcus pneumoniae was reported to be a virulence factor because of its specific hydrolysis activity toward the β(1,3)-linked galactose and N-acetylglucosamine (Galβ(1,3)NAG) moiety of oligosaccharides on the host molecules. Here we report the crystal structure of BgaC at 1.8 Å and its complex with galactose at 1.95 Å. At pH 5.5-8.0, BgaC exists as a stable homodimer, each subunit of which consists of three distinct domains: a catalytic domain of a classic (β/α)(8) TIM barrel, followed by two all-β domains (ABDs) of unknown function. The side walls of the TIM β-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 Trp-243 and Tyr-455. Simulation of a putative substrate entrance tunnel and modeling of a complex structure with Galβ(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 Trp-240 and Tyr-455 contribute to stabilizing the N-acetylglucosamine moiety, whereas Trp-243 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.

PubMed: 22593580
DOI: 10.1074/jbc.M112.367128

Experimental method

X-RAY DIFFRACTION (1.8 Å)