2f41: Difference between revisions
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'''Crystal structure of FapR- a global regulator of fatty acid biosynthesis in B. subtilis''' | {{Structure | ||
|PDB= 2f41 |SIZE=350|CAPTION= <scene name='initialview01'>2f41</scene>, resolution 2.50Å | |||
|SITE= | |||
|LIGAND= | |||
|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- a global regulator of fatty acid biosynthesis in B. subtilis''' | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
2F41 is a [ | 2F41 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=2F41 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: Buschiazzo, A.]] | [[Category: Buschiazzo, A.]] | ||
[[Category: Guerin, M E.]] | [[Category: Guerin, M E.]] | ||
[[Category: | [[Category: hot-dog fold]] | ||
''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 16:47:56 2008'' | ||
Revision as of 14:47, 20 March 2008
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| 2f41, resolution 2.50Å | |||||||||||||
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| Gene: | fapR (Bacillus subtilis) | ||||||||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||||||||
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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