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Catalytic Site Atlas

CSA LITERATURE entry for 1et0

E.C. nameaminodeoxychorismate lyase
SpeciesEscherichia coli (Bacteria)
E.C. Number (IntEnz) 4.1.3.38
CSA Homologues of 1et0
CSA Entries With UniProtID P28305
CSA Entries With EC Number 4.1.3.38
PDBe Entry 1et0
PDBSum Entry 1et0
MACiE Entry M0305

Literature Report

Introduction4-Amino-4-Deoxychorismate Lyase (ADCL), sourced from Escherichia coli is a member of the fold-type IV of PLP dependent enzymes. It converts 4-amino-4-deoxychorismate (ADC) to p-aminobenzoate and pyruvate. P-aminobenzoate is a precursor of folic acid. ADCL is a homodimer and shows the re-face specific hydrogen transfer typical of a member of the fold-type IV family.
Mechansim1. Lys 159 forms a Schiff base linkage to PLP, attaching it to the active site. 2. The amino group of ADC nucleophilically attacks the C4' of PLP. This forms a PLP-ADC Schiff base linkage and releases Lys 159. Lys 159 forms a hydrogen bond with Thr 38, decreasing the free energy level of the external aldimine form of the enzyme.The hydroxyl of Thr 38 makes a van der Waals contact with the methylene group of ADC. 3. The alpha-carbon of the substrate is activated by the protonated Schiff base and the protonated pyridine ring. Lys 159 acts as a general base and removes the alpha-proton of the alpha-carbon. This results in a quinonoid intermediate. 4. The quinonoid intermediate is stabilised by the delocalization of the cofactor-substrate Pi-system and the hydrogen bond between N1-H of the cofactor ring and Glu 193. 5. Thr 38 acts as a general acid and protonates the olefin moiety, causing electrons to migrate towards the substrate from the cofactor. This results in release of pyruvate with aromatization of the six-membered ring of the substrate. 6. Lys 159 nucleophilically attacks the C4' of PLP. This forms a PLP-Lys 159 Schiff base linkage and releases the substrate.
Reaction

Catalytic Sites for 1et0

Annotated By Reference To The Literature - Site 3 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
ThrA3828macie:sideChainThr 38 acts as a general acid and protonates the olefin moiety.
GluA193173macie:sideChainGlu 193 hydrogen bonds to the N1-H of the cofactor ring, helping to stabilise the quinonoid intermediate.
LysA159140macie:sideChainLys 159 forms a Schiff base linkage to PLP, attaching it to the active site. It also acts as a general base and removes the alpha-proton of the alpha-carbon. Lys 159 releases the substrate from the PLP-ADC Schiff base linkage at the end of the reaction.

Literature References

Notes:
Nakai T
Three-dimensional structure of 4-amino-4-deoxychorismate lyase from Escherichia coli.
J Biochem 2000 128 29-38
PubMed: 10876155
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