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Publication Abstract from PubMed

Site-specific covalent conjugation offers a powerful tool to identify and understand protein-protein interactions. In this study, we discover that sulfur fluoride exchange (SuFEx) warheads effectively crosslink the Escherichia coli acyl carrier protein (AcpP) with its partner BioF, a key pyridoxal 5'-phosphate (PLP)-dependent enzyme in the early steps of biotin biosynthesis by targeting a tyrosine residue proximal to the active site. We identify the site of crosslink by MS/MS analysis of the peptide originating from both partners. We further evaluate the BioF-AcpP interface through protein crystallography and mutational studies. Among the AcpP-interacting BioF surface residues, three critical arginine residues appear to be involved in AcpP recognition so that pimeloyl-AcpP can serve as the acyl donor for PLP-mediated catalysis. These findings validate an evolutionary gain-of-function for BioF, allowing the organism to build biotin directly from fatty acid biosynthesis through surface modifications selective for salt bridge formation with acidic AcpP residues.

Visualizing the Interface of Biotin and Fatty Acid Biosynthesis through SuFEx Probes.,Chen A, Re RN, Davis TD, Tran K, Moriuchi YW, Wu S, La Clair JJ, Louie GV, Bowman ME, Clarke DJ, Mackay CL, Campopiano DJ, Noel JP, Burkart MD J Am Chem Soc. 2024 Jan 17;146(2):1388-1395. doi: 10.1021/jacs.3c10181. Epub 2024 , Jan 4. PMID:38176024^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.