Porphobilinogen synthase (PBGS), which is also called delta-aminolevulinic acid dehydratase (ALAD), catalyzes the condensation of two 5-aminolevulinic acid (ALA) molecules to form the pyrrole porphobilinogen (PBG), which is the second step in the biosynthesis of tetrapyrroles, such as heme, vitamin B12 and chlorophyll. This reaction involves the formation of a Schiff base link between the substrate and the enzyme. PBGSs are metalloenzymes, some of which have a second, allosteric metal binding site, beside the metal ion binding site in their active site. Although PBGS is a family of homologous enzymes, its metal ion utilization at catalytic site varies between zinc and magnesium and/or potassium. PBGS can be classified into two groups based on differences in their active site metal binding site. All of PBGS_aspartate_rich contain an aspartate rich metal binding site with the general sequence DXALDX(Y/F)X3G(H/Q)DG. They also contain an allosteric magnesium binding sequence RX~164DX~65EXXXD and are activated by magnesium and/or potassium, but not by zinc. PBGSs_aspartate_rich are found in some bacterial species and photosynthetic organisms such as vascular plants, mosses and algae, but not in archaea.
Structure:1GZG_A, Pseudomonas Aeruginosa, ALAD_PBGS_asparate_rich; complex of active site with the inhibitor 5-Fluorolevulinic acid
Comment:The active site of ALAD contains A-site and P-site, each binding one molecule of 5-aminolevulinic acid (ALA); the A-site contains the metal ion binding site
Jiyao W et al.(2023). "The conserved domain database in 2023.",