View the latest EBI news stories and important announcements...

Search The CSA
EC Number

Catalytic Site Atlas

CSA LITERATURE entry for 1h7o

E.C. nameporphobilinogen synthase
SpeciesSaccharomyces cerevisiae (Baker's yeast)
E.C. Number (IntEnz)
CSA Homologues of 1h7oThere are 38 Homologs
CSA Entries With UniProtID P05373
CSA Entries With EC Number
PDBe Entry 1h7o
PDBSum Entry 1h7o
MACiE Entry 1h7o

Literature Report

Introduction5-Aminolaevulinic acid dehydratase (porphobilinogen synthase; EC catalyses the dimerisation of two molecules of 5-aminolaevulinic acid to give porphobilinogen in a Knorr-type pyrrole synthesis. Porphobilinogen is the pyrrole precursor utilised by all living systems for the biosynthesis of tetrapyrroles, including haems, chlorophylls and corrins.
MechansimTwo key lysine residues are located close to one another in the active and play a co-ordinated role in the mechanism of porphobilinogen synthesis, via formation of two Schiff bases with the two substrates. First P-side ALA binds and forms a Schiff base intermediate between C4 and one active site lysine (Lys263). This formally generates a water molecule, which is free to leave the open active site. A-side ALA binds next and forms a Schiff base intermediate between C4 and the adjacent active site lysine (Lys210). The next step in the reaction appears to be the formation of a bond between C3 of A-side ALA and C4 of P-side ALA, accompanied by the loss of one proton from C3 of A-side ALA. To complete formation of the pyrrole ring, the penultimate step in the reaction is a transfer of C4 of A-side ALA from its Schiff base with the active site lysine to a chemically comparable linkage with the C5-amino moiety of P-side ALA. This generates an almost-pyrrole intermediate. The final step in the PBGS catalyzed reaction is the binding of P-side ALA to an adjacent active site of the octamer, which is then accompanied by conformational changes that open the neighboring active site lid, which is accompanied by the breakdown of the covalent 'almost-product' complex and release of porphobilinogen. The residues performing general acid/base functions are yet to be formally identified.

Catalytic Sites for 1h7o

Annotated By Reference To The Literature - Site 1 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
LysA210210macie:sideChainForms a Schiff base linkage with substrate via nucleophilic arttack on carbonyl group. Reaction proceeds as above.
LysA263263macie:sideChainForms a Schiff base linkage with substrate via nucleophilic arttack on carbonyl group. Reaction proceeds as above.

Literature References

Erskine PT
The x-ray structure of yeast 5-aminolaevulinic acid dehydratase complexed with substrate and three inhibitors.
J Mol Biol 2001 312 133-141
PubMed: 11545591
Frère F
Structure of porphobilinogen synthase from Pseudomonas aeruginosa in complex with 5-fluorolevulinic acid suggests a double Schiff base mechanism.
J Mol Biol 2002 320 237-247
PubMed: 12079382