OASS shares the same fold with tryptophan synthase (TRPS) from Salmonella typhimurium but the sequence identity level is below 20%. There are some major structural differences: the loops providing the interface to the alpha-subunit in TRPS and two surface helices of TRPS are missing in OASS. The hydrophobic channel for indole transport from the  to the  active site of TRPS is, not unexpectedly, also absent in OASS. The dimer interface, on the other hand, is more or less conserved in the two enzymes.

Covalent binding of L-methionine as an external aldimine to the PLP-cofactor in the K41A mutant of OASS induces a large conformational change in the protein. Methionine mimics the action of the substrate OAS during catalysis. The carboxylate moiety of methionine forms a hydrogen bonding network to the "asparagine-loop" which adopts a different conformation than in the native protein. The local rearrangement acts as a trigger to induce a large global conformational change in the protein. The "movable subdomain" rotates towards the active site by a rotation of 7 °. This subdomain movement reduces the active site entrance to a small hole, giving access only to small molecules like sulfide, the second substrate, or acetate, the first product.

When chloride (and presumably sulfide) binds to OASS this results in a new "inhibited" conformation, that differs from the "open" native or "closed" external aldimine conformations. The allosteric binding site is located at the OASS dimer interface. The new "inhibited" structure involves a change in the position of the "movable domain" (residues 87-131) to a location that differs from that in the "open" or "closed" forms. The "inhibited" conformation prevents the substrate-binding loop from interacting with the carboxylate, and hinders formation of the external Schiff base and thus subsequent chemistry. These results suggest that OASS represents a new class of PLP-dependent enzymes that is regulated by small anions.