2f3x
From Proteopedia
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| - | [[Image:2f3x.gif|left|200px]] | + | [[Image:2f3x.gif|left|200px]] |
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| - | '''Crystal structure of FapR (in complex with effector)- a global regulator of fatty acid biosynthesis in B. subtilis''' | + | {{Structure |
| + | |PDB= 2f3x |SIZE=350|CAPTION= <scene name='initialview01'>2f3x</scene>, resolution 3.100Å | ||
| + | |SITE= | ||
| + | |LIGAND= <scene name='pdbligand=MLC:MALONYL-COENZYME A'>MLC</scene> | ||
| + | |ACTIVITY= | ||
| + | |GENE= fapR ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1423 Bacillus subtilis]) | ||
| + | }} | ||
| + | |||
| + | '''Crystal structure of FapR (in complex with effector)- a global regulator of fatty acid biosynthesis in B. subtilis''' | ||
| + | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 2F3X is a [ | + | 2F3X is a [[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=2F3X OCA]. |
==Reference== | ==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:[http:// | + | 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:[http://www.ncbi.nlm.nih.gov/pubmed/16932747 16932747] |
[[Category: Bacillus subtilis]] | [[Category: Bacillus subtilis]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
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[[Category: Guerin, M E.]] | [[Category: Guerin, M E.]] | ||
[[Category: MLC]] | [[Category: MLC]] | ||
| - | [[Category: | + | [[Category: hot-dog fold / malonyl-coa complex]] |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 16:47:49 2008'' |
Revision as of 14:47, 20 March 2008
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| , resolution 3.100Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | |||||||
| Gene: | fapR (Bacillus subtilis) | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal structure of FapR (in complex with effector)- 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
2F3X 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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