Development of Zn(II) Hydroxide Complexes Containing N2S Donor Atom Sets: Molecular Motifs of the Active Site of Peptide Deformylase
Dr. Eric Brown
The function of the metalloenzyme peptide deformylase (PDF) is to deformylate proteins that contain N-formylated methionine. Since this is unique to prokaryotes, elucidation of the detailed mechanism of how PDF works may be important for antibiotic design. In Eubacteria, protein synthesis is initiated by a special transfer-RNA charged with N-formylmethionine which blocks the reactive amino group preventing unfavorable side reactions. This is specific only to prokaryotes and removal of the formyl group as the polypeptide exits the ribosomal tunnel is essential for protein synthesis to continue. Failure to deformylate the amino terminal will cause the formyl group to be buried causing incorrect folding of the proteins. Motivation for studying the mechanism comes from the unusual finding that the most active form of PDF is not a zinc-containing enzyme but instead an iron-containing enzyme. In order to explain the unusual metal dependency, we have prepared two new N2S ligands (ligand A and B), which have been shown by X-ray crystallography to form mononuclear Zn(II)-Br complexes. These N2S ligands model the cysteine and two histidine binding motif present in the active site of PDF but have unique features that are expected to result in mononuclear iron complexes. Details of the synthetic procedures and characterization data of our Zn(II) complexes is presented.
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