Non-coding nucleotides and amino acids near the active site regulate peptide deformylase expression and inhibitor susceptibility in Chlamydia trachomatis
| Autor: | Niseema Pachikara, Christopher B. Oey, Amit Balakrishnan, Huizhou Fan, Xiaofeng Bao, Bryce E. Nickels, Theodore Chase, Lars F. Westblade, Ming Tan |
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| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
Transcription
Genetic 5' Flanking Region Chlamydia trachomatis Biology medicine.disease_cause Microbiology Amidohydrolases 03 medical and health sciences Peptide deformylase Transcription (biology) Catalytic Domain Gene expression Drug Resistance Bacterial Enzyme Stability medicine Humans Enzyme Inhibitors Promoter Regions Genetic Pathogen 030304 developmental biology chemistry.chemical_classification 0303 health sciences Base Sequence 030306 microbiology Point mutation Dipeptides Gene Expression Regulation Bacterial Molecular biology Standard 3. Good health Amino acid Kinetics Enzyme chemistry Biochemistry Amino Acid Substitution Mutation Cell and Molecular Biology of Microbes HeLa Cells |
| Zdroj: | Bao, X; Pachikara, ND; Oey, CB; Balakrishnan, A; Westblade, LF; Tan, M; et al.(2011). Non-coding nucleotides and amino acids near the active site regulate peptide deformylase expression and inhibitor susceptibility in Chlamydia trachomatis. Microbiology, 157(9), 2569-2581. doi: 10.1099/mic.0.049668-0. UC Irvine: Retrieved from: http://www.escholarship.org/uc/item/4h59k1fg Microbiology |
| Popis: | Chlamydia trachomatis,an obligate intracellular bacterium, is a highly prevalent human pathogen. Hydroxamic-acid-based matrix metalloprotease inhibitors can effectively inhibit the pathogen bothin vitroandin 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. |
| Databáze: | OpenAIRE |
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