Target analysis of α-alkylidene-γ-butyrolactones in uropathogenic E. coli.

Abstract:

:α-Alkylidene-γ-butyrolactones are quite common in nature and exhibit a broad spectrum of biological activities. We therefore synthesized a small library of xanthatine inspired α-alkylidene-γ-butyrolactones to screen non-pathogenic and uropathogenic E. coli strains by activity based protein profiling (ABPP). The identified targets are involved in cellular redox processes and give first insight into the preferred binding sites of this privileged motif. Furthermore the gene of one protein, c2450, which was only identified in uropathogenic E. coli belongs to a genomic island which encodes a hybrid polyketide/non-ribosomal peptide synthetase (PKS/NRPS). This system is responsible for the synthesis of colibactin, a natural product which causes DNA double strand breaks in eukaryotic cells leading to the activation of the DNA damage checkpoint pathway and subsequent cell cycle arrest. While the role of several proteins that are involved in the colibactin synthesis has been elucidated, the function of c2450 remains elusive. Investigation of the binding site showed that c2450 is modified at a cysteine residue which may be important for the catalytic activity.

journal_name

Mol Biosyst

journal_title

Molecular bioSystems

authors

Kunzmann MH,Sieber SA

doi

10.1039/c2mb25313e

subject

Has Abstract

pub_date

2012-11-01 00:00:00

pages

3061-7

issue

11

eissn

1742-206X

issn

1742-2051

journal_volume

8

pub_type

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