Molecular basis for Tay-Sachs revealed by the crystal structure of human β-hexosaminidaseA

Abstract

environmental contaminants. Here we present the crystal structure of the terminal oxygenase component of the biphenyl dioxygenase (BphA1A2) derived from Rhodococcus strain sp. RHA1. This is the first crystal structure of the biphenyl dioxygenase. We also determined the crystal structure of the BphA1A2-biphenyl complex. Structural comparison between the substrate free and complex forms revealed that the substrate-binding pocket makes significant conformational changes upon substrate binding to accommodate the substrate into the pocket. The analysis with the two crystal structures suggested that the residues in the substrate-binding pocket can be classified into three groups, which respectively seem to be responsible for the catalytic reaction, the orientation/conformation of the substrate, and the conformational changes of the substrate-binding pocket.