2f41
From Proteopedia
(New page: 200px<br /><applet load="2f41" size="450" color="white" frame="true" align="right" spinBox="true" caption="2f41, resolution 2.50Å" /> '''Crystal structure of...) |
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| - | [[Image:2f41.jpg|left|200px]]<br /><applet load="2f41" size=" | + | [[Image:2f41.jpg|left|200px]]<br /><applet load="2f41" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="2f41, resolution 2.50Å" /> | caption="2f41, resolution 2.50Å" /> | ||
'''Crystal structure of FapR- a global regulator of fatty acid biosynthesis in B. subtilis'''<br /> | '''Crystal structure of FapR- a global regulator of fatty acid biosynthesis in B. subtilis'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Malonyl-CoA is an essential intermediate in fatty acid synthesis in all | + | 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. |
==About this Structure== | ==About this Structure== | ||
| - | 2F41 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Bacillus_subtilis Bacillus subtilis]. Full crystallographic information is available from [http:// | + | 2F41 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Bacillus_subtilis Bacillus subtilis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2F41 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Bacillus subtilis]] | [[Category: Bacillus subtilis]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Alzari, P | + | [[Category: Alzari, P M.]] |
[[Category: Buschiazzo, A.]] | [[Category: Buschiazzo, A.]] | ||
| - | [[Category: Guerin, M | + | [[Category: Guerin, M E.]] |
[[Category: 'hot-dog' fold]] | [[Category: 'hot-dog' fold]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:17:32 2008'' |
Revision as of 15:17, 21 February 2008
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Crystal structure of FapR- a global regulator of fatty acid biosynthesis in B. subtilis
Overview
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.
About this Structure
2F41 is a Single protein structure of sequence from Bacillus subtilis. Full crystallographic information is available from OCA.
Reference
Structural basis of lipid biosynthesis regulation in Gram-positive bacteria., Schujman GE, Guerin M, Buschiazzo A, Schaeffer F, Llarrull LI, Reh G, Vila AJ, Alzari PM, de Mendoza D, EMBO J. 2006 Sep 6;25(17):4074-83. Epub 2006 Aug 24. PMID:16932747
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