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Catalytic Site Atlas

CSA LITERATURE entry for 1w27

E.C. namephenylalanine ammonia-lyase
SpeciesPetroselinum crispum (Petroselinum hortense)
E.C. Number (IntEnz) 4.3.1.24
CSA Homologues of 1w27
CSA Entries With UniProtID P24481
CSA Entries With EC Number 4.3.1.24
PDBe Entry 1w27
PDBSum Entry 1w27
MACiE Entry 1w27

Literature Report

IntroductionPhenylalanine ammonia-lyase (PAL) is a plant enzyme catalyzes the non-oxidative elimination of ammonia from L-Phe to give trans-cinnamate. Trans-cinnamate is the precursor of numerous phenylpropanoid compounds and plays an important role in plant development and plant stress response. PAL may become a useful palliative for phenylketonuria as it has been shown to be able to convert excess Phe (toxic) in the blood into harmless compounds.
MechansimThe electrophile in the mechanism is thought to be formed by the autocatalytic formation of 3,5-dihydro-5-methyldiene-4H-imidazole-4-one group (MIO) from the tripeptide Ala202-Ser203-Gly204. The MIO group is formed by cyclisation as a result of two water elimination steps. The sp3 conformation at Gly204 amide N increases the electrophicity of the Ser203 beta-C atom.
In the reaction mechanism, an electron pair of the substrate phenyl ring attacks the beta-C of Ser203 of the MIO causing the MIO to become aromatic. The conversion of MIO to the aromatic state changes the conformation of Gly204 amide-N from sp3 to sp2, causing a small peptide displacement.
The Ser203 oxygen anion produced stabilises the positively charged sigma-complex of the substrate phenyl group. The positive charge is also stabilised by an interaction with the pi-electrons of Phe400. The electron-deficient phenyl ring of L-Phe renders the two hydrogen atoms at the beta-C atom of the substrate acidic. Tyr351' from another subunit abstracts the pro-S beta-hydrogen from the substrate.
The rearrangement of the Phe-MIO adduct eliminates the amino group and regenerates MIO. The resulting ammonia is released into the solvent after the trans-cinnamate has diffused away.
The proton abstracted by Tyr351' can be easily released to the bulk solvent to regenerate the enzyme.
Reaction

Catalytic Sites for 1w27

Annotated By Reference To The Literature - Site 3 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
PheA400400macie:sideChainPhe400 stabilises the positively charged sigma-complex intermediate to prevent the removal of the proton in the ortho-position of the aromatic ring.
TyrB351351macie:sideChainTyr351' acts as a base, abstracting a beta-H from the substrate.The proton is released into the bulk solvent.

Annotated By Reference To The Literature - Site 4 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
PheB400400macie:sideChainError

Annotated By Reference To The Literature - Site 5 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
PheA400400macie:sideChainPhe400 stabilises the positively charged sigma-complex intermediate to prevent the removal of the proton in the ortho-position of the aromatic ring.
TyrB351351macie:sideChainTyr351' acts as a base, abstracting a beta-H from the substrate.The proton is released into the bulk solvent.

Annotated By Reference To The Literature - Site 6 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
TyrA351351macie:sideChainError

Literature References

Notes:
Ritter H
Structural basis for the entrance into the phenylpropanoid metabolism catalyzed by phenylalanine ammonia-lyase.
Plant Cell 2004 16 3426-3436
PubMed: 15548745
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