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2f3x
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(New page: 200px<br /><applet load="2f3x" size="450" color="white" frame="true" align="right" spinBox="true" caption="2f3x, resolution 3.100Å" /> '''Crystal structure o...)
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Revision as of 08:13, 21 November 2007
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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 with MLC as ligand. 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
Page seeded by OCA on Wed Nov 21 10:21:04 2007
