Iron-sulfur cluster-binding SPASM domain of coenzyme PQQ synthesis protein E
Coenzyme PQQ synthesis protein E (PqqE), also called pyrroloquinoline quinone (PQQ) biosynthesis protein E or PqqA peptide cyclase (EC 22.214.171.124), is a radical S-adenosylmethionine (SAM) enzyme that catalyzes the formation of a C-C bond between C-4 of glutamate and C-3 of tyrosine residues of the PqqA protein, which is the first enzymatic step in the biosynthesis of the bacterial enzyme cofactor PQQ. Radical SAM enzymes are characterized by a conserved CxxxCxxC motif, which coordinates the conserved iron-sulfur cluster that is involved in the reductive cleavage of SAM and generates a 5'-deoxyadenosyl radical, which in turn abstracts a hydrogen from the appropriately positioned carbon atom of the substrate. Radical SAM (RS) enzymes with a C-terminal SPASM domain contain at least one other iron-sulfur cluster. PqqE contains two auxiliary Fe-S clusters in its SPASM domain: one nearest the RS site (AuxI) is in the form of a 2Fe-2S cluster ligated by four cysteines; and a more remote cluster (AuxII) in the form of a 4Fe-4S center that is ligated by three cysteine residues and one aspartate residue.