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| {{STRUCTURE_2f41| PDB=2f41 | SCENE= }} | | {{STRUCTURE_2f41| PDB=2f41 | SCENE= }} |
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| '''Crystal structure of FapR- a global regulator of fatty acid biosynthesis in B. subtilis'''
| | ===Crystal structure of FapR- a global regulator of fatty acid biosynthesis in B. subtilis=== |
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| ==Overview==
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| Malonyl-CoA is an essential intermediate in fatty acid synthesis in all living cells. Here we demonstrate a new role for this molecule as a global regulator of lipid homeostasis in Gram-positive bacteria. Using in vitro transcription and binding studies, we demonstrate that malonyl-CoA is a direct and specific inducer of Bacillus subtilis FapR, a conserved transcriptional repressor that regulates the expression of several genes involved in bacterial fatty acid and phospholipid synthesis. The crystal structure of the effector-binding domain of FapR reveals a homodimeric protein with a thioesterase-like 'hot-dog' fold. Binding of malonyl-CoA promotes a disorder-to-order transition, which transforms an open ligand-binding groove into a long tunnel occupied by the effector molecule in the complex. This ligand-induced modification propagates to the helix-turn-helix motifs, impairing their productive association for DNA binding. Structure-based mutations that disrupt the FapR-malonyl-CoA interaction prevent DNA-binding regulation and result in a lethal phenotype in B. subtilis, suggesting this homeostatic signaling pathway as a promising target for novel chemotherapeutic agents against Gram-positive pathogens.
| | The line below this paragraph, {{ABSTRACT_PUBMED_16932747}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 16932747 is the PubMed ID number. |
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| | {{ABSTRACT_PUBMED_16932747}} |
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| ==About this Structure== | | ==About this Structure== |
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| [[Category: Guerin, M E.]] | | [[Category: Guerin, M E.]] |
| [[Category: Hot-dog fold]] | | [[Category: Hot-dog fold]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 03:26:14 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 16:25:34 2008'' |
