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8XJU

Cryo-EM structure of colibactin assembly line polyketide synthase ClbI (apo state)

Summary for 8XJU
Entry DOI10.2210/pdb8xju/pdb
EMDB information38406
DescriptorPolyketide synthase (1 entity in total)
Functional Keywordscolibactin, microbiome, polyketide synthase, colorectal cancer, nrps-pks hybrid, biosynthetic protein, transferase
Biological sourceEscherichia coli
Total number of polymer chains2
Total formula weight221305.48
Authors
Kim, M.,Kim, J.,Kang, J.Y. (deposition date: 2023-12-22, release date: 2025-05-21, Last modification date: 2025-05-28)
Primary citationKim, M.,Kim, J.,Lee, G.S.,Olinares, P.D.B.,Airan, Y.,Chow, J.L.,Park, J.,Jeong, Y.,Park, J.,Chait, B.T.,Herzon, S.B.,Kim, C.S.,Kang, J.Y.
Structural study on human microbiome-derived polyketide synthases that assemble genotoxic colibactin.
Structure, 2025
Cited by
PubMed Abstract: Colibactin, a human microbiome-derived genotoxin, promotes colorectal cancer by damaging the host gut epithelial genomes. While colibactin is synthesized via a hybrid non-ribosomal peptide synthetase (NRPS)-polyketide synthase (PKS) pathway, known as pks or clb, the structural details of its biosynthetic enzymes remain limited, hindering our understanding of its biosynthesis and clinical application. In this study, we report the cryo-EM structures of two colibactin-producing PKS enzymes, ClbC and ClbI, captured in different reaction states using a substrate-mimic crosslinker. Our structural analysis revealed the binding sites of carrier protein (CP) domains of the ClbC and ClbI on their ketosynthase (KS) domains. Further, we identified a novel NRPS-PKS docking interaction between ClbI and its upstream enzyme, ClbH, mediated by the C-terminal peptide ClbH and the dimeric interface of ClbI, establishing a 1:2 stoichiometry. These findings advance our understanding of colibactin assembly line and provide broader insights into NRPS-PKS natural product biosynthesis mechanisms.
PubMed: 40381618
DOI: 10.1016/j.str.2025.04.017
PDB entries with the same primary citation
Experimental method
ELECTRON MICROSCOPY (2.91 Å)
Structure validation

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