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Search The CSA
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Catalytic Site Atlas

CSA LITERATURE entry for 1kl7

E.C. namethreonine synthase
SpeciesSaccharomyces cerevisiae (Baker's yeast)
E.C. Number (IntEnz) 4.2.3.1
CSA Homologues of 1kl7
CSA Entries With UniProtID P16120
CSA Entries With EC Number 4.2.3.1
PDBe Entry 1kl7
PDBSum Entry 1kl7
MACiE Entry 1kl7

Literature Report

IntroductionThreonine synthase (TS) from Saccharomyces cerevisiae catalyses the conversion of O-phospho-L-homoserine (OPHS) into threonine and phosphate. This is the final step in threonine biosynthesis. The enzyme requires a pyridoxal 5'-phosphate (PLP) cofactor which binds at the interface of all three of the protein's domains.
MechansimThe catalytic cycle starts with a transaldimination reaction. Lys124 which is initially bound to the PLP cofactor is replaced by OPHS forming the external aldimine. Lys124 catalyses the abstraction of the C-alpha proton of the substrate and its transfer to the PLP C4' position. Next, Lys124 stereospecifically abstracts the beta-pro-S hydrogen leading to the non-hydrolytic elimination of the gamma-phosphate. The gamma-methylene group left after the elimination is reprotonated producing the PLP-derivative of E-aminocrotonate. Next, water is added at C-beta. Finally, reverse transaldimination yields L-threonine.
Reaction

Catalytic Sites for 1kl7

Annotated By Reference To The Literature - Site 1 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
LysA124124macie:sideChainLys124 is the only residue in the immediate environment of the bound substrate that can act as an acid-base catalyst. It is involved in the abstraction of a proton from C-alpha and it's transfer to C4' as well as the abstraction of a proton from C-beta and the protonation of the C-gamma in the methylene intermediate. In the last step, Lys124 acts as a nucleophile attacking the external aldimine resulting in the release of the L-threonine.

Annotated By Reference To The Literature - Site 2 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
LysB124124macie:sideChainLys124 is the only residue in the immediate environment of the bound substrate that can act as an acid-base catalyst. It is involved in the abstraction of a proton from C-alpha and it's transfer to C4' as well as the abstraction of a proton from C-beta and the protonation of the C-gamma in the methylene intermediate. In the last step, Lys124 acts as a nucleophile attacking the external aldimine resulting in the release of the L-threonine.

Literature References

Notes:The enzyme-substrate complex could not be crystallised and the position of the substrate in the enzyme monomer was modelled based on the binding of aminoethoxy vinylglycine in cystathionine beta-lyase. For the initial transaldimination reaction to occur, the amino group on the OPHS substrate needs to be deprotonated. The pH optimum for TS is 8.2 and the concentration of deprotonated OPHS in solution should account for the observed reaction rate without the need for deprotonation of the substrate by specific residues in the active site.
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