6anr

Crystal structure of a self resistance protein ClbS from colibactin biosynthetic gene cluster

spinqualitylabelsall models 6anr, resolution 2.10Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6anr 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 2.098Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function Q0P7K8_ECOLX Publication Abstract from PubMed Certain commensal Escherichia coli contain the clb biosynthetic gene cluster that codes for small molecule prodrugs known as precolibactins. Precolibactins are converted to colibactins by N-deacylation; the latter are postulated to be genotoxic and to contribute to colorectal cancer formation. Though advances toward elucidating (pre)colibactin biosynthesis have been made, the functions and mechanisms of several clb gene products remain poorly understood. Here we report the 2.1 A X-ray structure and molecular function of ClbS, a gene product that confers resistance to colibactin toxicity in host bacteria and which has been shown to be important for bacterial viability. The structure harbors a potential colibactin binding site and shares similarity to known hydrolases. In vitro studies using a synthetic colibactin analog and ClbS or an active site residue mutant reveal cyclopropane hydrolase activity that converts the electrophilic cyclopropane of the colibactins into an innocuous hydrolysis product. As the cyclopropane has been shown to be essential for genotoxic effects in vitro, this ClbS-catalyzed ring-opening provides a means for the bacteria to circumvent self-induced genotoxicity. Our study provides a molecular-level view of the first reported cyclopropane hydrolase and support for a specific mechanistic role of this enzyme in colibactin resistance. ClbS Is a Cyclopropane Hydrolase That Confers Colibactin Resistance.,Tripathi P, Shine EE, Healy AR, Kim CS, Herzon SB, Bruner SD, Crawford JM J Am Chem Soc. 2017 Dec 13;139(49):17719-17722. doi: 10.1021/jacs.7b09971. Epub, 2017 Nov 28. PMID:29112397 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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