Human cystathionine beta-synthase (CBS) is unique in bearing not only a catalytically important pyridoxal-5'-phosphate (PLP) but also heme. We have observed the alternation of heme environment under the alkaline condition causes the inactivation of CBS. On the basis of crystal structure, we propose that the change in the axial ligation of heme would modulate CBS activity through the interaction with Arg-266.