2013.04.11，我院陈宇星教授和周丛照教授研究组在Journal of Biological Chemistry上发表论文：Structural insights into the substrate specificity of a 6-phospho-β-glucosidase BglA-2 from Streptococcus pneumoniae TIGR4. J Biol Chem. 2013 Apr 11. [Epub ahead of print]

作　者：余维丽、江永亮、Pikis A、成望、柏晓辉、任艳敏、Thompson J、周丛照、陈宇星。

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 (G6P). 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 Å 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: Tyr126, Tyr303 and Trp338 at subsite +1 of BglA-2, determine substrate specificity with respect to (1,4)-linked 6-phospho-β-glucosides. Moreover, three additional residues: Ser424, Lys430 and Tyr432 of BglA-2, were found to play important roles in the hydrolytic selectivity towards 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 differences between the structurally similar 6-phospho-β-galactosidases and 6-phospho-β-glucosidases assigned to GH-1 family.