4IPN

The complex structure of 6-phospho-beta-glucosidase BglA-2 with thiocellobiose-6P from Streptococcus pneumoniae

Summary for 4IPN

• Entry DOI: 10.2210/pdb4ipn/pdb
• Related: 4IPL
• Related PRD ID: PRD_900096
• Descriptor: 6-phospho-beta-glucosidase, 6-O-phosphono-alpha-L-idopyranose-(1-4)-4-thio-beta-D-glucopyranose (3 entities in total)
• Functional Keywords: hydrolysase, hydrolase
• Biological source: Streptococcus pneumoniae
• Total number of polymer chains: 2
• Total formula weight: 113328.61

Authors

Yu, W.L.,Jiang, Y.L.,Andreas, P.,Cheng, W.,Bai, X.H.,Ren, Y.M.,Thompsonn, J.,Zhou, C.Z.,Chen, Y.X. (deposition date: 2013-01-10, release date: 2013-04-24, Last modification date: 2024-02-28)

Primary citation

Yu, W.L.,Jiang, Y.L.,Pikis, A.,Cheng, W.,Bai, X.H.,Ren, Y.M.,Thompson, J.,Zhou, C.Z.,Chen, Y.
Structural insights into the substrate specificity of a 6-phospho-&[beta]-glucosidase BglA-2 from Streptococcus pneumoniae TIGR4
J.Biol.Chem., 288:14949-14958, 2013

PubMed Abstract: The 6-phospho-β-glucosidase BglA-2 (EC 3.2.1.86) from glycoside hydrolase family 1 (GH-1) catalyzes the hydrolysis of β-1,4-linked cellobiose 6-phosphate (cellobiose-6'P) to yield glucose and glucose 6-phosphate. Both reaction products are further metabolized by the energy-generating glycolytic pathway. Here, we present the first crystal structures of the apo and complex forms of BglA-2 with thiocellobiose-6'P (a non-metabolizable analog of cellobiose-6'P) at 2.0 and 2.4 Å resolution, respectively. Similar to other GH-1 enzymes, the overall structure of BglA-2 from Streptococcus pneumoniae adopts a typical (β/α)8 TIM-barrel, with the active site located at the center of the convex surface of the β-barrel. Structural analyses, in combination with enzymatic data obtained from site-directed mutant proteins, suggest that three aromatic residues, Tyr(126), Tyr(303), and Trp(338), at subsite +1 of BglA-2 determine substrate specificity with respect to 1,4-linked 6-phospho-β-glucosides. Moreover, three additional residues, Ser(424), Lys(430), and Tyr(432) of BglA-2, were found to play important roles in the hydrolytic selectivity toward phosphorylated rather than non-phosphorylated compounds. Comparative structural analysis suggests that a tryptophan versus a methionine/alanine residue at subsite -1 may contribute to the catalytic and substrate selectivity with respect to structurally similar 6-phospho-β-galactosidases and 6-phospho-β-glucosidases assigned to the GH-1 family.

PubMed: 23580646
DOI: 10.1074/jbc.M113.454751

Experimental method

X-RAY DIFFRACTION (2.411 Å)