7mdc

Full-length wildtype ClbP inhibited by hexanoyl-D-asparagine boronic acid

spinqualitylabelsall models 7mdc, resolution 2.70Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7mdc is a 1 chain structure with sequence from Escherichia coli. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.7Å Ligands: 2PE, 97N, CL, DMS, SO4, YX7 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function Q0P7K6_ECOLX Publication Abstract from PubMed The human gut bacterial genotoxin colibactin is a possible key driver of colorectal cancer (CRC) development. Understanding colibactin's biological effects remains difficult owing to the instability of the proposed active species and the complexity of the gut microbiota. Here, we report small molecule boronic acid inhibitors of colibactin biosynthesis. Designed to mimic the biosynthetic precursor precolibactin, these compounds potently inhibit the colibactin-activating peptidase ClbP. Using biochemical assays and crystallography, we show that they engage the ClbP binding pocket, forming a covalent bond with the catalytic serine. These inhibitors reproduce the phenotypes observed in a clbP deletion mutant and block the genotoxic effects of colibactin on eukaryotic cells. The availability of ClbP inhibitors will allow precise, temporal control over colibactin production, enabling further study of its contributions to CRC. Finally, application of our inhibitors to related peptidase-encoding pathways highlights the power of chemical tools to probe natural product biosynthesis. A small molecule inhibitor prevents gut bacterial genotoxin production.,Volpe MR, Velilla JA, Daniel-Ivad M, Yao JJ, Stornetta A, Villalta PW, Huang HC, Bachovchin DA, Balbo S, Gaudet R, Balskus EP Nat Chem Biol. 2023 Feb;19(2):159-167. doi: 10.1038/s41589-022-01147-8. Epub 2022 , Oct 17. PMID:36253549 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Beta-lactamase 3D structures

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