The crystal structure of anthranilate synthase from Sulfolobus solfataricus: Functional implications

摘要

Anthranilate synthase catalyzes the synthe- sis of anthranilate from chorismate and glutaminc and is feedback-inhibited by tryptophan. The enzyme of thc hyper- thermophile Suffolobus solfataricus has been crystallized in the absence of physiological ligands, and its three-dimensional structure has been determined at 2.5-A resolution with x-ray crystallography. It is a heterotetramer of anthranilate syn- thase (TrpE) and glutamine amidotransferase (TrpG) sub- units, in which two TrpG:TrpE protomers associate mainly via the TrpG subunits. The small TrpG subunit (195 residues) has the known ''triad" glutamine amidotransferase fold. The large TrpE subunit (421 residues) has a novel fold. It displays a cleft between two domains, the tips of which contact the TrpG subunit across its active site. Clustcrs of catalytically essential residues are located inside the cleft, spatially separated from clustered residues involved in feedback inhibition. The struc- ture suggests a model in which chorismate binding triggers a relative movement of the two domain tips of the TrpE subunit, activating the TrpG subunit and creating a channel for passage of ammonia toward the active site of the TrpE subunit. Tryptophan presumably blocks this rearrangement, thus sta- bilizing the inactive states of both subunits. The structure of the TrpE subunit is a likely prototype for the related enzymes 4-amino 4-deoxychorismate spothase and isochorismate syn- thase.