Synthetic phosphoramidate analogues of nucleosides have been used as enzyme inhibitors for decades and have therapeutic applications in the treatments of HIV and cancer, but little is known about how N-P bonds are fashioned in nature. The heptapeptide MccA undergoes post-translational processing in producer strains of Escherichia coli to afford microcin C7 (MccC7), a "Trojan horse" antibiotic that contains a phosphoramidate linkage to adenosine monophosphate at its C-terminus. We show that the enzyme MccB, encoded by the MccC7 gene cluster, is responsible for formation of the N-P bond in MccC7. This modification requires the consumption of two ATP molecules per MccA peptide and formation and breakdown of a peptidyl-succinimide intermediate.
Synthetic pan class="Chemical">phosphoramidate analogues of n>an class="Chemical">nucleosides have been used as enzyme inhibitors for decades and have therapeutic applications in the treatments of HIV and cancer, but little is known about how N-P bonds are fashioned in nature. The heptapeptide MccA undergoes post-translational processing in producer strains of Escherichia coli to afford microcin C7 (MccC7), a "Trojan horse" antibiotic that contains a phosphoramidate linkage to adenosine monophosphate at its C-terminus. We show that the enzyme MccB, encoded by the MccC7 gene cluster, is responsible for formation of the N-P bond in MccC7. This modification requires the consumption of two ATP molecules per MccA peptide and formation and breakdown of a peptidyl-succinimide intermediate.
Authors: Inna Zukher; Maria Novikova; Anton Tikhonov; Mikhail V Nesterchuk; Ilya A Osterman; Marko Djordjevic; Petr V Sergiev; Cynthia M Sharma; Konstantin Severinov Journal: Nucleic Acids Res Date: 2014-10-01 Impact factor: 16.971
Authors: David J Gonzalez; Shaun W Lee; Mary E Hensler; Andrew L Markley; Samira Dahesh; Douglas A Mitchell; Nuno Bandeira; Victor Nizet; Jack E Dixon; Pieter C Dorrestein Journal: J Biol Chem Date: 2010-06-25 Impact factor: 5.157