The porphobilinogen synthase family of metalloenzymes

The porphobilinogen synthase (PBGS) family of enzymes catalyzes the first c ommon step in the biosynthesis of the essential tetrapyrroles such as chlor ophyll and porphyrin, Although PBGSs are highly conserved at ail four level s of protein structure, there is considerable diversity in the use of dival ent cations for the catalytically essential and allosteric roles. Assumptio ns regarding commonalities among the PBGS proteins coupled with the diversi ty of usage of metal ions has led to a confused literature. The recent publ ication of crystal structures for three PBGS proteins coupled with more tha n 50 individual PBGS sequences allows an evaluation of these assumptions. T his topical review focuses on the usage of metals by the PBGS family of pro teins. It raises doubt concerning a dogma that there has been an evolutiona ry shift between Zn-II and Mg-II at one or more of the divalent metal-bindi ng sites. It also raises the possibility that there may be up to four speci fic divalent metal ion-binding sites, each serving a unique function that c an be alternatively filled by amino acids in some of the PBGSs.