Indole-3-glycerol phosphate synthase (IGPS) (see <db_xref db="INTERPRO" dbkey="IPR001468"/>) catalyzes the fourth step in the biosynthesis of tryptophan, the ring closure of 1-(2-carboxy-phenylamino)-1-deoxyribulose into indol-3-glycerol-phosphate. In some bacteria, IGPS is a single chain enzyme. In others, such as <taxon tax_id="562">Escherichia coli</taxon>, it is the N-terminal domain of a bifunctional enzyme that also catalyzes N-(5-phosphoribosyl)anthranilate isomerase (PRAI) activity, the third step of tryptophan biosynthesis. In fungi, IGPS is the central domain of a trifunctional enzyme that contains a PRAI C-terminal domain and a glutamine amidotransferase (GATase) N-terminal domain (see <db_xref db="INTERPRO" dbkey="IPR000991"/>).<p> Phosphoribosylanthranilate isomerase (PRAI) is monomeric and labile in mostmesophilic microorganisms, but dimeric and stable in the hyperthermophile <taxon tax_id="2336">Thermotoga maritima</taxon> (tPRAI) [<cite idref="PUB00006524"/>]. The comparison to the known 2.0 A structure of PRAI from <taxon tax_id="562">Escherichia coli</taxon> (ePRAI) shows that tPRAI has the complete TIM- or (beta alpha)8-barrel fold, whereas helix alpha5 in ePRAI is replaced by a loop. The subunits of tPRAI associate via the N-terminal faces of their central beta-barrels. Two long, symmetry-related loops that protrude reciprocally into cavities of the other subunit provide for multiple hydrophobic interactions. Moreover, the side chains of the N-terminal methionines and the C-terminal leucines of both subunits are immobilized in a hydrophobic cluster, and the number of salt bridges is increased in tPRAI. These features appear to be mainly responsible for the high thermostability of tPRAI [<cite idref="PUB00006375"/>]. </p>