Identification of an allosteric anion-binding site on O-acetylserine sulfhydrylase: Structure of the enzyme with chloride bound

A new crystal structure of O-acetylserine sulfhydrylase (OASS) has been sol ved with chloride bound at an allosteric site and sulfate bound at the acti ve site. The bound anions result in a new "inhibited" conformation, that di ffers from the "open" native or "closed" external aldimine conformations. T he allosteric site is located at the OASS dimer interface. The new inhibite d structure involves a change in the position of the "moveable domain" (res idues 87-131) to a location that differs from that in the open or closed fo rms. Formation of the external aldimine with substrate is stabilized by int eraction of the alpha -carboxyl group of the substrate with a substrate-bin ding loop that is part of the moveable domain. The inhibited conformation p revents the substrate-binding loop from interacting with the alpha -carboxy l group, and hinders formation of the external Schiff base and thus subsequ ent chemistry. Chloride may be an analog of sulfide, the physiological inhi bitor. Finally, these results suggest that OASS represents a new class of P LP-dependent enzymes that is regulated by small anions. (C) 2000 Academic P ress.