2f41: Difference between revisions
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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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[[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 Sun May 4 03:26:14 2008'' | |||
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Revision as of 03:26, 4 May 2008
Crystal structure of FapR- a global regulator of fatty acid biosynthesis in B. subtilis
OverviewOverview
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 StructureAbout this Structure
2F41 is a Single protein structure of sequence from Bacillus subtilis. Full crystallographic information is available from OCA.
ReferenceReference
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 Page seeded by OCA on Sun May 4 03:26:14 2008