Fig. 7
From: Targeting adenylate-forming enzymes with designed sulfonyladenosine inhibitors
Biochemistry of E. coli microcin C7 synthetase MccB. The C-terminal carboxylate of the MccA precursor peptide (7.1) is adenylated to form a MccA-AMP intermediate (7.2), whose asparagine side-chain amide cyclizes to form a succinimide intermediate (7.3). MccB then catalyzes a second adenylation reaction to form a succinimide adenylate (7.4), which is hydrolyzed to form a phosphoramidate product (7.5). Downstream installation of an O-aminopropyl group provides microcin C (7.6). This Trojan horse antibiotic is taken up by target cells via peptide transporters, then the N-terminal peptide is proteolyzed to form an aspartyl-phosphoramidate (7.7), which inhibits aspartyl-tRNA synthetases in the target cell. R = fMRTGNA = N-formyl-Met-Arg-Thr-Gly-Asn-Ala peptide
