Catalysis and regulation of cyclic dinucleotide specific phosphodiesterases
In recent years, cyclic-di-GMP (c-di-GMP) has been firmly established as a major bacterial second messenger; whereas the structurally similar c-di-AMP has also emerged as another previously hidden messenger in prokaryotes. How the degradation of c-di-GMP and c-di-AMP is catalyzed and regulated remai...
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| Format: | Thesis |
| Language: | English |
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2011
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| Online Access: | https://hdl.handle.net/10356/43545 |
| _version_ | 1824453863552319488 |
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| author | Rao, Feng |
| author2 | Liang Zhao-Xun |
| author_facet | Liang Zhao-Xun Rao, Feng |
| author_sort | Rao, Feng |
| collection | NTU |
| description | In recent years, cyclic-di-GMP (c-di-GMP) has been firmly established as a major bacterial second messenger; whereas the structurally similar c-di-AMP has also emerged as another previously hidden messenger in prokaryotes. How the degradation of c-di-GMP and c-di-AMP is catalyzed and regulated remains poorly understood. We elucidated the catalytic mechanism of RocR, an EAL-domain containing c-di-GMP specific phosphodiesterase (PDE) from the opportunistic pathogen P. aeruginosa. We identified a conserved functional loop that is critical for the enzymatic activity and likely to be involved in the regulation of EAL domain. In addition, we discovered that the DHH domain-containing protein YybT is an efficient c-di-AMP-specific PDE. The PAS domain of YybT was unexpectedly found to bind them and regulate the PDE activity in response to them or nitric oxide. These biochemical and biophysical results not only yielded insight into the catalytic and regulatory mechanisms of the cyclic dinucleotide degrading proteins, but also unearthed a large number of catalytic inactive EAL domain protein from the bacterial genomes. |
| first_indexed | 2025-02-19T03:13:11Z |
| format | Thesis |
| id | ntu-10356/43545 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2025-02-19T03:13:11Z |
| publishDate | 2011 |
| record_format | dspace |
| spelling | ntu-10356/435452023-02-28T18:49:00Z Catalysis and regulation of cyclic dinucleotide specific phosphodiesterases Rao, Feng Liang Zhao-Xun School of Biological Sciences DRNTU::Science::Biological sciences::Microbiology::Bacteria In recent years, cyclic-di-GMP (c-di-GMP) has been firmly established as a major bacterial second messenger; whereas the structurally similar c-di-AMP has also emerged as another previously hidden messenger in prokaryotes. How the degradation of c-di-GMP and c-di-AMP is catalyzed and regulated remains poorly understood. We elucidated the catalytic mechanism of RocR, an EAL-domain containing c-di-GMP specific phosphodiesterase (PDE) from the opportunistic pathogen P. aeruginosa. We identified a conserved functional loop that is critical for the enzymatic activity and likely to be involved in the regulation of EAL domain. In addition, we discovered that the DHH domain-containing protein YybT is an efficient c-di-AMP-specific PDE. The PAS domain of YybT was unexpectedly found to bind them and regulate the PDE activity in response to them or nitric oxide. These biochemical and biophysical results not only yielded insight into the catalytic and regulatory mechanisms of the cyclic dinucleotide degrading proteins, but also unearthed a large number of catalytic inactive EAL domain protein from the bacterial genomes. DOCTOR OF PHILOSOPHY (SBS) 2011-03-31T01:34:30Z 2011-03-31T01:34:30Z 2010 2010 Thesis Rao, F. (2010). Catalysis and regulation of cyclic dinucleotide specific phosphodiesterases. Doctoral thesis, Nanyang Technological University, Singapore. https://hdl.handle.net/10356/43545 10.32657/10356/43545 en 150 p. application/pdf |
| spellingShingle | DRNTU::Science::Biological sciences::Microbiology::Bacteria Rao, Feng Catalysis and regulation of cyclic dinucleotide specific phosphodiesterases |
| title | Catalysis and regulation of cyclic dinucleotide specific phosphodiesterases |
| title_full | Catalysis and regulation of cyclic dinucleotide specific phosphodiesterases |
| title_fullStr | Catalysis and regulation of cyclic dinucleotide specific phosphodiesterases |
| title_full_unstemmed | Catalysis and regulation of cyclic dinucleotide specific phosphodiesterases |
| title_short | Catalysis and regulation of cyclic dinucleotide specific phosphodiesterases |
| title_sort | catalysis and regulation of cyclic dinucleotide specific phosphodiesterases |
| topic | DRNTU::Science::Biological sciences::Microbiology::Bacteria |
| url | https://hdl.handle.net/10356/43545 |
| work_keys_str_mv | AT raofeng catalysisandregulationofcyclicdinucleotidespecificphosphodiesterases |