Summary: N-(5'phosphoribosyl)anthranilate (PRA) isomerase
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Phosphoribosylanthranilate isomerase Edit Wikipedia article
3D rendering of Phosophoribosylanthranilate Isomerase
|PDB structures||RCSB PDB PDBe PDBsum|
|Gene Ontology||AmiGO / QuickGO|
In yeast it is encoded by the TRP1 gene.
This enzyme belongs to the family of isomerases, specifically those intramolecular oxidoreductases interconverting aldoses and ketoses. The systematic name of this enzyme class is N-(5-phospho-beta-D-ribosyl)anthranilate aldose-ketose-isomerase. Other names in common use include:
- PRA isomerase,
- IGPS:PRAI (indole-3-glycerol-phosphate,
- synthetase/N-5'-phosphoribosylanthranilate isomerase complex), and
- N-(5-phospho-beta-D-ribosyl)anthranilate ketol-isomerase.
- xPRAI (monomeric variant in Saccharmyces cerevisiae)
- PRAI[ML256-452] (engineered variant of 1-(2-carboxy-phenylamino)-1-deoxy-D-ribulose 5-phosphate carboxylase: PRAI)
Phosphoribosylanthranilate isomerase is one of the many enzymes within the biosynthesis pathway of tryptophan (an essential amino acid). The upstream* pathway substrates and intermediates are shown below (Fig. 2).
As seen in Fig. 3, N-(5'-phosphoribosyl)-anthranilate via this enzyme is converted into 1-(o-carboxyphenylamino)-1-deoxribulose 5-phosphate. As the name phosphoribosylanthranilate isomerase suggests, it functions as an isomerase, rearranging the parts of the molecule without adding or removing molecules or atoms.
The reaction seen in Fig. 3, is an intramolecular redox (reduction-oxidation) reaction. Its first step involves a proton transfer. This product intermediate, an enolamine, is fluorescent, which is useful for kinetic studies
within this pathway. However, this product is unstable, and quickly isomerases into an Î±-amino keto.
- Note: Upstream/Downstream are relative to the compounds/molecules directly involved in phosphoribosylanthranilate isomerase reaction
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 Î²Î± loops are responsible for the activity of this enzyme, and the Î±Î² 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.
Specifically, for phosphoribosyl anthranilate isomerase, TkTrpF, from Thermococcus kodakaraensis. The active site for the Amadori rearrangement, was determined to be Cys8 (acting as the general base) and Asp135 (as the general acid).
Reduced 1-(2-carboxyphenylamino )-1-deoxy-D-ribulose 5-phosphate [5, 6,8); Indoleglycerol phosphate (8); Indolepropanol phosphate (8); MnCI2 CoCI2 [16); CuS04 (16); More (chemically synthesized N-(5-phospho-betaD-ribosyl)anthranilate contains inhibitors, but not if it is generated by anthranilate phosphoribosyltransferase)
26300 (Bacillus subtilis, gel filtration)
45000 (Aeromonas formicans, Serratia marinorubra, gel filtration, indole-3-
glycerol-phosphate synthetase/N-5'-phosphoribosylanthranilate isomerase
46000 (E. coli, sedimentation equilibrium)
47000 (Citrobacter ballerupensis, gel filtration, indole-3-glycerol-phosphate
synthetase/N-5'-phosphoribosylanthranilate isomerase complex)
48000 (Serratia marcescens , Erwinia carotovora , gel filtration , indole-3-glycerol-phosphate synthetase/N-5'-phosphoribosylanthranilate
isomerase complex )
49370 (E. coli, calculated from gene sequence)
53000 (Proteus vulgaris, gel filtration, indole-3-glycerol-phosphate synthetase/
N-5'-phosphoribosylanthranilate isomerase complex)
160000 (Neurospora crassa, gel filtration, component lib of the anthranilate
synthetase complex has N-(5'-phosphoribosyl)anthranilate isomerase and
indole-3-glycerol phosphate synthetase activities)
185000 (Hansenula henricii, gel filtration, indole-3-glycerol-phosphate synthetase/
N-5'-phosphoribosylanthranilate isomerase complex)
A list of genes encoding for PRAI can also be found on KEGG Enzyme database.
- Creighton TE, Yanofsky C (1970). "Chorismate to tryptophan (Escherichia coli) - Anthranilate synthetase, PR transferase, PRA isomerase, InGP synthetase, tryptophan synthetase". Methods Enzymol. Methods in Enzymology. 17A: 365â€“380. doi:10.1016/0076-6879(71)17215-1. ISBN 9780121818746.
- "TRP1/YDR007W Summary". Saccharomyces genome database. Stanford University.
- Schomburg, Dietmar; Stephan, DÃ¶rte (1994). Enzyme handbook. Springer-Verlag. ISBN 9783642579424. OCLC 859587801.
- Lubert Stryer (2019-03-25). Biochemistry. ISBN 9781319114657. OCLC 1052398743.
- Hommel U, Eberhard M, Kirschner K (April 1995). "Phosphoribosyl anthranilate isomerase catalyzes a reversible amadori reaction". Biochemistry. 34 (16): 5429â€“39. doi:10.1021/bi00016a014. PMID 7727401.
- Sterner R, Merz A, Thoma R, Kirschner K (2001). "Phosphoribosylanthranilate isomerase and indoleglycerol-phosphate synthase: tryptophan biosynthetic enzymes from Thermotoga maritima". Methods in Enzymology. 331: 270â€“80. doi:10.1016/S0076-6879(01)31064-9. ISBN 9780121822323. PMID 11265469.
- Perveen, S.; Rashid, N.; Papageorgiou, A.C. (2016-11-09). "Phosphoribosyl anthranilate isomerase from Thermococcus kodakaraensis". doi:10.2210/pdb5lhf/pdb. Cite journal requires
- Thoma R, Hennig M, Sterner R, Kirschner K (March 2000). "Structure and function of mutationally generated monomers of dimeric phosphoribosylanthranilate isomerase from Thermotoga maritima". Structure. 8 (3): 265â€“76. doi:10.1016/s0969-2126(00)00106-4. PMID 10745009.
- Hennig M, Sterner R, Kirschner K, Jansonius JN (May 1997). "Crystal structure at 2.0 A resolution of phosphoribosyl anthranilate isomerase from the hyperthermophile Thermotoga maritima: possible determinants of protein stability". Biochemistry. 36 (20): 6009â€“16. doi:10.1021/bi962718q. PMID 9166771.
- Eberhard M, Tsai-Pflugfelder M, Bolewska K, Hommel U, Kirschner K (April 1995). "Indoleglycerol phosphate synthase-phosphoribosyl anthranilate isomerase: comparison of the bifunctional enzyme from Escherichia coli with engineered monofunctional domains". Biochemistry. 34 (16): 5419â€“28. doi:10.1021/bi00016a013. PMID 7727400.
- doi:10.1016/0022-2836(92)90665-7. PMID 1738159. ; Wilmanns M, Priestle JP, Niermann T, Jansonius JN (January 1992). "Three-dimensional structure of the bifunctional enzyme phosphoribosylanthranilate isomerase: indoleglycerolphosphate synthase from Escherichia coli refined at 2.0 A resolution". Journal of Molecular Biology. 223 (2): 477â€“507.
- Pitt, Charles (2002). Sax, Adolphe (opera). Oxford Music Online. Oxford University Press. doi:10.1093/gmo/9781561592630.article.o006145.
- "Enzymeâ†’ Inhibitor List: M", Handbook of Enzyme Inhibitors, Wiley-VCH Verlag GmbH, 1999, pp. 894â€“956, doi:10.1002/9783527618330.ch13, ISBN 9783527618330
- "Blast search for phosphoribosylanthranilate isomerase". HomoloGene Database. National Center for Biotechnology Information.
- "KEGG Enzyme".
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N-(5'phosphoribosyl)anthranilate (PRA) isomerase Provide feedback
No Pfam abstract.
Wilmanns M, Priestle JP, Niermann T, Jansonius JN; , J Mol Biol 1992;223:477-507.: Three-dimensional structure of the bifunctional enzyme phosphoribosylanthranilate isomerase: indoleglycerolphosphate synthase from Escherichia coli refined at 2.0 A resolution. PUBMED:1738159 EPMC:1738159
Internal database links
External database links
This tab holds annotation information from the InterPro database.
InterPro entry IPR001240
N-(5'-phosphoribosyl) anthranilate isomerase (PRAI) is an enzyme that catalyses the third step of tryptophan biosynthesis. Proteins containing this domain include N-(5'-phosphoribosyl) anthranilate isomerase, anthranilate synthase component 2 and the tryptophan biosynthesis protein TRP1.
Phosphoribosylanthranilate isomerase is monomeric and labile in most mesophilic microorganisms, but dimeric and stable in the hyperthermophile Thermotoga maritima (tPRAI) [PUBMED:10745009]. The comparison to the known 2.0 A structure of PRAI from Escherichia coli (ePRAI) shows that tPRAI has the complete TIM- or (beta alp ha)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 [PUBMED:9166771].
The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.
|Molecular function||phosphoribosylanthranilate isomerase activity (GO:0004640)|
|Biological process||tryptophan metabolic process (GO:0006568)|
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This large superfamily of TIM barrel enzymes all contain a common phosphate binding site. The phosphate is found in a variety of cofactors and ligands such as FMN [1,2].
The clan contains the following 59 members:4HFCP_synth Ala_racemase_N ALAD Aldolase AP_endonuc_2 BtpA CdhD ComA CutC DAHP_synth_1 DAHP_synth_2 DeoC DHDPS DHO_dh DHquinase_I DUF2090 DUF561 DUF692 DUF993 Dus F_bP_aldolase FMN_dh G3P_antiterm Glu_syn_central Glu_synthase His_biosynth HMGL-like IGPS IMPDH KDGP_aldolase Lys-AminoMut_A MtrH NanE NAPRTase NeuB NMO OAM_alpha OMPdecase Orn_Arg_deC_N Oxidored_FMN PcrB PdxJ PRAI PRMT5_TIM Pterin_bind QRPTase_C Radical_SAM RhaA Ribul_P_3_epim SOR_SNZ Tagatose_6_P_K TAL_FSA ThiC_Rad_SAM ThiG TIM TMP-TENI Trp_syntA UvdE UxuA
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1Cannot generate PP/Heatmap alignments for seeds; no PP data available
Key: available, not generated, — not available.
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|Seed source:||Pfam-B_247 (release 2.1)|
|Number in seed:||18|
|Number in full:||6650|
|Average length of the domain:||193.70 aa|
|Average identity of full alignment:||30 %|
|Average coverage of the sequence by the domain:||70.47 %|
|HMM build commands:||
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 45638612 -E 1000 --cpu 4 HMM pfamseq
|Family (HMM) version:||22|
|Download:||download the raw HMM for this family|
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There are 2 interactions for this family. More...
We determine these interactions using iPfam, which considers the interactions between residues in three-dimensional protein structures and maps those interactions back to Pfam families. You can find more information about the iPfam algorithm in the journal article that accompanies the website.
For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the PRAI domain has been found. There are 14 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein sequence.
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