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http://hdl.handle.net/10603/430151
Title: | Characterization of the transsulfuration enzyme Cystathionine beta synthase as a novel regulatory node in the sulfur metabolism of Mycobacterium tuberculosis |
Researcher: | Bandyopadhyay, Parijat |
Guide(s): | Singh, Amit |
Keywords: | Genetics and Heredity Life Sciences Molecular Biology and Genetics |
University: | Indian Institute of Science Bangalore |
Completed Date: | 2021 |
Abstract: | Methionine and cysteine metabolisms are important for the survival and pathogenesis of Mycobacterium tuberculosis (Mtb). The transsulfuration pathway converts methionine to cysteine and represents an important link between antioxidant and methylation metabolism in diverse organisms. Using a combination of biochemistry and cryo-electron microscopy, we characterized the first enzyme of the transsulfuration pathway, cystathionine and#946;-synthase (MtbCbs) in Mtb. We demonstrated that MtbCbs is a heme-less, pyridoxal-5 -phosphate (PLP) containing enzyme, allosterically activated by S-adenosylmethionine (SAM). The atomic model of MtbCbs in its native and SAM bound conformations revealed a unique mode of SAM dependent allosteric activation and tetramerization. Further, SAM stabilized MtbCbs by sterically occluding proteasomal degradation, which was crucial for supporting methionine and redox metabolism in Mtb. Genetic deficiency of MtbCbs reduced Mtb survival upon homocysteine overload in vitro, inside macrophages, and in mice co-infected with HIV. Thus, the MtbCbs-SAM axis constitutes an important mechanism of coordinating sulfur metabolism in Mtb. newline |
Pagination: | xix, 180 |
URI: | http://hdl.handle.net/10603/430151 |
Appears in Departments: | Microbiology and Cell Biology |
Files in This Item:
File | Description | Size | Format | |
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01_title.pdf | Attached File | 77.71 kB | Adobe PDF | View/Open |
02_prelim pages.pdf | 1.06 MB | Adobe PDF | View/Open | |
03_table of content.pdf | 136.91 kB | Adobe PDF | View/Open | |
04_abstract.pdf | 248.5 kB | Adobe PDF | View/Open | |
05_chapter 1.pdf | 2.33 MB | Adobe PDF | View/Open | |
06_chapter 2.pdf | 2.13 MB | Adobe PDF | View/Open | |
07_chapter 3.pdf | 1.9 MB | Adobe PDF | View/Open | |
08_chapter 4.pdf | 1.62 MB | Adobe PDF | View/Open | |
09_chapter 5.pdf | 1.3 MB | Adobe PDF | View/Open | |
10_chapter 6.pdf | 678.85 kB | Adobe PDF | View/Open | |
11_annexure.pdf | 417.73 kB | Adobe PDF | View/Open | |
80_recommendation.pdf | 256.59 kB | Adobe PDF | View/Open |
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