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CSA entry for 1nsj
Original Entry
Title:
Isomerase
Compound:
Phosphoribosyl anthranilate isomerase
Mutant:
No
UniProt/Swiss-Prot:
Q56320-TRPF_THEMA
EC Class:
5.3.1.24
Other CSA Entries:
Overview of all sites for 1nsj
Homologues of 1nsj
Entries for UniProt/Swiss-Prot: Q56320
Entries for EC: 5.3.1.24
Other Databases:
PDB entry: 1nsj
PDBsum entry: 1nsj
UniProt/Swiss-Prot: Q56320
IntEnz entry: 5.3.1.24
Literature Report:
Introduction:
Phosphoribosyl anthranilate isomerase is a key enzyme in the biosynthesis of tryptophan, catalysing the interconversion of the aminoaldose phosphoribosyl anthranilate (PRA) and the aminoketose 1-[(2-carboxyphen-yl) amino]-1-deoxyribulose 5-phosphate (CdRP). It shares significant structural and sequence homology to other aldose-ketose isomerases, notably the analogous enzyme in the Histidine biosynthesis pathway, HisA which catalyses a similar reaction. The two are assumed to follow the same mechanism, namely Amadori rearrangement with acid base catalysis.
Mechanism:
The general mechanism for this reaction is an Amadori rearrangement. Protonation of the ribosyl ring oxygen by Cys 7 results in ring opening and formation of an imine intermediate. This intermediate is electrophilic due to the positive charge on the nitrogen, so deprotonation of C2 by Asp 126 can occur, leading to the formation of the enol tautomer of the product, which rapidly tautomerises to the keto form, the product CdRP.
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Found by:
Literature reference 

ResidueChainNumberUniProt numberFunctional part FunctionTargetDescription
CYSA 7 7Sidechain
Acid/baseSubstrate
Acts as general acid to protonate the ribosyl ring oxygen, precipitating ring opening and the formation of the electrophilic imino intermediate.
Evidence from paper Evidence concerns Evidence type
PubMed ID 12356303 Current protein Residue is positioned appropriately (ligand position known)
PubMed ID 12356303 Current protein Mutagenesis of residue
PubMed ID 12356303 Current protein Structural similarity to homologue of known mechanism
PubMed ID 12356303 Current protein pH dependence of reaction

ResidueChainNumberUniProt numberFunctional part FunctionTargetDescription
ASPA 126 126Sidechain
Acid/baseSubstrate
Acts as general base to deprotonate C2 of the ribosyl moiety leading to the formation of the enol of CdRP.
Evidence from paper Evidence concerns Evidence type
PubMed ID 12356303 Current protein Residue is positioned appropriately (ligand position known)
PubMed ID 12356303 Current protein Mutagenesis of residue
PubMed ID 12356303 Current protein Structural similarity to homologue of known mechanism
References:
1
Two (betaalpha)(8)-barrel enzymes of histidine and tryptophan biosynthesis have similar reaction mechanisms and common strategies for protecting their labile substrates.
M. Henn-Sax and R. Thoma and S. Schmidt and M. Hennig and K. Kirschner and R. Sterner
Biochemistry 41, (40) 12032-42, (2002).
12356303
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