InterPro: IPR002283 Isopenicillin N synthase

Isopenicillin N synthase (IPNS) is a nonhaem-Fe²⁺-dependent enzyme that belongs to a class of nonhaem Fe²⁺-containing enzymes, which includes 2-oxoglutarate-dependent dioxygenases, 2-oxoglutarate-dependent hydroxy- lases, and enzymes involved in ethylene formation and anthocyaninidin biosynthesis. IPNS catalyses the stereospecific formation of the beta-lactam and thiazolidine rings of IPN via a 4-electron oxidation of the tripeptide ACV. The enzyme uses, as the sole electron acceptor, one molecule of dioxygen, which is completely reduced to two molecules of water. The oxygen stoichiometry shown by IPNS is the same as that for cytochrome C oxidase, but is unusual for nonhaem-iron-containing enzymes, which typically catalyse the transfer of one or both atoms of dioxygen into their substrates. IPNS thus provides an interesting contrast to dioxygenase enzymes.

All IPNS proteins reported to date have a molecular mass of 30-40kDa and are highly conserved. The degree of identity in the predicted amino acid sequence ranges from 54-75%. Two cysteines are invariant in all known IPNS sequences; these residues are believed to be functionally important for iron binding. Histidine and aspartic acid residues in the sequence constitute the endogenous ligands of the ferrous active site.