We report the X-ray crystal structure of a glycoside hydrolase family 43 beta-xylosidase, RS223BX, which is strongly activated by the addition of divalent metal cations. The 2.69 structure reveals that the Ca2+ cation is located at the back of the active-site pocket. The Ca2+ is held in the active site by the carboxylate of D85, an "extra" acid residue in comparison to other GH43 active sites. The Ca2+ is in close contact with a histidine imidazole, which in turn is in contact with the catalytic base (D15) thus providing a mechanism for stabilizing the carboxylate anion of the base and achieve metal activation. The active-site pocket is mirrored by an "inactive-site" pocket of unknown function that resides on the opposite side of the monomer.