Indole-3-glycerol phosphate synthase (IGPS; TrpC; EC 4.1.1.48), the enzyme catalyzing the fourth step of L-tryptophan biosynthesis. It converts 1-(2-carboxyphenylamino)-1-deoxy-D-ribulose 5-phosphate (CdRP) into (1S,2R)-1-C-(indol-3-yl)glycerol 3-phosphate (indole-3-glycerol phosphate, IGP), releasing CO2 and water in an irreversible decarboxylative ring-closure reaction. This indole-ring-forming step lies downstream of anthranilate phosphoribosyltransferase (TrpD) and upstream of the tryptophan synthase subunits (TrpA/TrpB). The protein adopts a classic (beta/alpha)8 TIM-barrel (ribulose-phosphate-binding barrel) fold and acts as a soluble cytoplasmic metabolic enzyme. In Pseudomonas putida KT2440 the gene (PP_0422) lies in the trpGDC operon, and loss-of-function insertions cause tryptophan auxotrophy. The enzyme family is highly conserved across bacteria and has no human homolog.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000162 L-tryptophan biosynthetic process | IEA GO_REF:0000120 | ACCEPT | Summary: TrpC/IGPS catalyzes the fourth step of L-tryptophan biosynthesis; this process annotation is correct and represents a core function of the gene. Reason: Matches the UniProt-curated pathway annotation (L-tryptophan from chorismate, step 4/5) and is supported by tryptophan-auxotrophy phenotypes of PP_0422 insertion mutants in P. putida KT2440. This is a core function. |
| GO:0004425 indole-3-glycerol-phosphate synthase activity | IEA GO_REF:0000120 | ACCEPT | Summary: This is the canonical molecular function of TrpC, matching the UniProt RecName (Indole-3-glycerol phosphate synthase, EC 4.1.1.48) and the curated catalytic activity (CdRP to indole-3-glycerol phosphate + CO2 + H2O). Reason: Directly supported by UniProt HAMAP-Rule MF_00134, InterPro IGPS domain signatures (IPR001468/IPR013798/IPR045186), EC 4.1.1.48 and RHEA:23476. Core molecular function. |
| GO:0004640 phosphoribosylanthranilate isomerase activity | IEA GO_REF:0000118 | REMOVE | Summary: Phosphoribosylanthranilate isomerase (PRAI, TrpF, EC 5.3.1.24) catalyzes the third step of tryptophan biosynthesis and is a distinct activity from IGPS. This activity is NOT supported for P. putida KT2440 TrpC by UniProt, which assigns only IGPS (EC 4.1.1.48). The annotation is a TreeGrafter over-propagation arising because some bacteria (e.g. E. coli) have a bifunctional TrpC(F) protein, whereas in Pseudomonas TrpF is a separate gene. Reason: UniProt Q88QR6 (HAMAP MF_00134) annotates only the monofunctional IGPS activity (277 aa, single IGPS domain), with no PRAI/TrpF domain. The IEA TreeGrafter inference reflects the bifunctional TrpCF architecture of some lineages and is not applicable to this monofunctional Pseudomonas enzyme. This is an electronic (IEA) prediction argued against on biological/domain grounds, not the second-guessing of an experimental annotation. |
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Download this section (compressed HTML)Q: Has the IGPS activity of P. putida KT2440 TrpC (PP_0422) been biochemically characterized (kcat/KM), or is the assignment based solely on homology and the auxotrophy phenotype?
Experiment: Purify recombinant PP_0422 and measure IGPS activity (CdRP to IGP) to confirm the monofunctional assignment and exclude any cryptic PRAI activity.
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