@article {Velilla2022,
	title = {Structural basis of colibactin activation by the ClbP peptidase},
	journal = {Nature Chemical Biology},
	year = {2022},
	month = {Oct},
	abstract = {Colibactin, a DNA cross-linking agent produced by gut bacteria, is implicated in colorectal cancer. Its biosynthesis uses a prodrug resistance mechanism: a non-toxic precursor assembled in the cytoplasm is activated after export to the periplasm. This activation is mediated by ClbP, an inner-membrane peptidase with an N-terminal periplasmic catalytic domain and a C-terminal three-helix transmembrane domain. Although the transmembrane domain is required for colibactin activation, its role in catalysis is unclear. Our structure of full-length ClbP bound to a product analog reveals an interdomain interface important for substrate binding and enzyme stability and interactions that explain the selectivity of ClbP for the N-acyl-d-asparagine prodrug motif. Based on structural and biochemical evidence, we propose that ClbP dimerizes to form an extended substrate-binding site that can accommodate a pseudodimeric precolibactin with its two terminal prodrug motifs in the two ClbP active sites, thus enabling the coordinated activation of both electrophilic warheads.},
	issn = {1552-4469},
	doi = {10.1038/s41589-022-01142-z},
	url = {https://doi.org/10.1038/s41589-022-01142-z},
	author = {Velilla, Jos{\'e} A. and Volpe, Matthew R. and Kenney, Grace E. and Walsh, Richard M. and Balskus, Emily P. and Gaudet, Rachelle}
}
