1887

Abstract

an obligate intracellular bacterium, is a highly prevalent human pathogen. Hydroxamic-acid-based matrix metalloprotease inhibitors can effectively inhibit the pathogen both and , and have exhibited therapeutic potential. Here, we provide genome sequencing data indicating that peptide deformylase (PDF) is the sole target of the inhibitors in this organism. We further report molecular mechanisms that control chlamydial PDF (cPDF) expression and inhibition efficiency. In particular, we identify the σ-dependent promoter that controls cPDF gene expression and demonstrate that point mutations in this promoter lead to resistance by increasing cPDF transcription. Furthermore, we show that substitution of two amino acids near the active site of the enzyme alters enzyme kinetics and protein stability.

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2011-09-01
2019-12-05
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Supplements

vol. , part 9, pp. 2569 - 2581

Supplementary tables [PDF](87 kb): Details of the cPDF gene and CTL0608 components and related materials Sequences of primers used for identification and confirmation of the PDF gene transcription initiation site



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