Synthesis of plantazolicin analogues enables dissection of ligand binding interactions of a highly selective methyltransferase.
A convergent strategy for the synthesis of truncated analogues of plantazolicin (PZN), a member of the thiazole/oxazole-modified microcin (TOMM) class of natural products, has been developed. These N-terminal mono-, tri-, and pentazole substructures of PZN were utilized to probe the substrate requirements and thermodynamic ligand binding parameters of an unusually selective PZN methyltransferase (BamL) by isothermal titration calorimetry. Our results demonstrate that the presence of a single N-terminal azole permits efficient processing by BamL; however, the substrate binding becomes stronger with increased polyazole chain length.
Department of Chemistry, Institute for Genomic Biology, Department of Microbiology, University of Illinois at Urbana-Champaign , Urbana, Illinois 61801, United States.
Abhishek
A
Sharma
Patricia M B
PMB
Saint-Vincent
Douglas A
DA
Mitchell
D000595:Amino Acid Sequence; D001430:Bacteriocins / Q000737:chemistry; D001665:Binding Sites; D002151:Calorimetry; D008024:Ligands; D008780:Methyltransferases / Q000737:chemistry* / Q000378:metabolism; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000737:chemistry*; D010080:Oxazoles / Q000737:chemistry; D013816:Thermodynamics; D013844:Thiazoles / Q000737:chemistry
D001430:Bacteriocins; D008024:Ligands; D009842:Oligopeptides; D010080:Oxazoles; D013844:Thiazoles; C560834:plantazolicin A; C560835:plantazolicin B; C020411:microcin; D008780:Methyltransferases