page_title: Phosphoribosylanthranilate isomerase
section_title: Structure
hierarchical_section_title: Phosphoribosylanthranilate isomerase / Structure
caption_attribution_description: English: PRAI
context_page_description: In enzymology, a phosphoribosylanthranilate isomerase [ PRAI ] is an enzyme that catalyzes the third step of the synthesis of the amino acid tryptophan.
  This enzyme participates in the phenylalanine, tyrosine and tryptophan biosynthesis pathway, also known as the aromatic amino acid biosynthesis pathway
  In yeast it is encoded by the TRP1 gene.
context_section_description: Depending on the microorganism PRAI's structure can vary between a mono-functional enzyme (monomeric and labile) or a stable bi-functional dimeric enzyme. Within Saccharomyces cerevisiae, Bacillus subtilis, Pseudomonas putida, and Acinetobacter calcoaceticus the enzyme is monmeric. In contrast, in hyperthermophile Thermotoga maritima, Escherichia coli (Fig. 5), Salmonella typhimurium, and Aerobacter aerogenes, and Serratia marcescens, it is a bi-functional enzyme with indoleglycerol phosphate synthase as the paired enzyme.
  
  The crystal structure has been characterized for a variety of the above listed microorganisms. The known 2.0 A structure of PRAI from Pyrococcus furiosus shows that tPRAI has a TIM-barrel fold (Fig. 6). PRAI derived from Thermococcus kodakaraensis also expresses a similar TIM-barrel fold structure. 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.
  The bi-functional version of this enzyme isolated from E. Coli (Fig. 5) performs two steps within the Tryptophan pathway. Referencing Fig. 7, the N-terminal catalyzes the IGPS reaction (residues ~1–289 purple), and the C-terminal domain performs the PRAI reaction (residues ~158–452 turquoise). Although these domains overlap (orange), the active sites are not overlapping, and studies have shown that mono-functional enzymes composing of these two domains are still able to produce a functional tryptophan bio-synthetic pathway.
  The βα loops are responsible for the activity of this enzyme, and the αβ loops are involved in the protein's stability.
  More details on the discovery of this enzyme's structure can be found in Willmann's paper.
caption: Fig 5: Three dimensional structure of the bi-functional PRAI: IGPS enzyme from E. Coli
    Fig 7: IGPS (purple), shared (orange), and PRAI (turquoise) reaction domains
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