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EC Number

Catalytic Site Atlas

CSA LITERATURE entry for 1a50

E.C. nametryptophan synthase
SpeciesSalmonella typhimurium (Bacteria)
E.C. Number (IntEnz)
CSA Homologues of 1a50There are 56 Homologs
CSA Entries With UniProtID P00929
CSA Entries With EC Number
PDBe Entry 1a50
PDBSum Entry 1a50
MACiE Entry 1a50

Literature Report

IntroductionTryptophan synthase is a pyridoxal 5'-phosphate-dependent (PLP-dependent) alpha-2-beta-2 complex catalysing the last two steps of tryptophan biosynthesis in bacteria, plants and fungi (but not in animals, where it is an essential component of the diet). It was the first enzyme for which a product formed at one site was demonstrated to be intramolecularly transferred to another site.
MechansimThe reaction takes place at two different sites, known as the alpha-site (on the A chain) and the beta-site (on the B chain). The product from the alpha site is transferred through a tunnel to the beta site. The overall reaction at the alpha-site is Indole-3-glycerol phosphate -> Indole + D-Glyceraldehyde-3-phosphate. The overall reaction at the beta-subunit is Indole + L-Serine -> L-Tryptophan. The reaction at the alpha-site proceeds through general acid/base catalysis. The reaction at the beta-site proceeds through many intermediates, as detected by fluorescence studies – for a detailed overview, see Scheme 1 in reference 19387555.

Catalytic Sites for 1a50

Annotated By Reference To The Literature - Site 1 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
GluA4949macie:sideChainProtonates C3 of indole. Subsequently accepts hydroxyl proton of glycerophosphate.
AspA6060macie:sideChainStabilises charge development on IGP indole ring during C-C bond scission.
LysB8787macie:sideChainBinds PLP. Abstracts the alpha-proton of the external aldimine and protonates the tryptophan quinonoid intermediate.
GluB109109macie:sideChainAccepts proton from alpha-amine of L-serine. Donates proton to leaving hydroxide. Stabilises charges developing on indole nitrogen during formation of indole quinonoid.

Literature References

Schiaretti F
pH dependence of tryptophan synthase catalytic mechanism: I. The first stage, the beta-elimination reaction.
J Biol Chem 2004 279 29572-29582
PubMed: 15117965
Raboni S
Tryptophan synthase: a mine for enzymologists.
Cell Mol Life Sci 2009 66 2391-2403
PubMed: 19387555
Dunn MF
Tryptophan synthase: the workings of a channeling nanomachine.
Trends Biochem Sci 2008 33 254-264
PubMed: 18486479
Catalytic mechanism of the tryptophan synthase alpha(2)beta(2) complex. Effects of pH, isotopic substitution, and allosteric ligands.
J Biol Chem 1999 274 31189-31194
PubMed: 10531312