Non-coding nucleotides and amino acids near the active site regulate peptide deformylase expression and inhibitor susceptibility in Chlamydia trachomatis. Academic Article uri icon

Overview

abstract

  • Chlamydia trachomatis, an obligate intracellular bacterium, is a highly prevalent human pathogen. Hydroxamic-acid-based matrix metalloprotease inhibitors can effectively inhibit the pathogen both in vitro and in vivo, 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 σ⁶⁶-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.

publication date

  • June 30, 2011

Research

keywords

  • Amidohydrolases
  • Chlamydia trachomatis
  • Gene Expression Regulation, Bacterial

Identity

PubMed Central ID

  • PMC3352175

Scopus Document Identifier

  • 80052377663

Digital Object Identifier (DOI)

  • 10.1128/JB.00480-06

PubMed ID

  • 21719536

Additional Document Info

volume

  • 157

issue

  • Pt 9