2f41
From Proteopedia
| Line 7: | Line 7: | ||
|ACTIVITY= | |ACTIVITY= | ||
|GENE= fapR ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1423 Bacillus subtilis]) | |GENE= fapR ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1423 Bacillus subtilis]) | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY=[[2f3x|2F3X]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2f41 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2f41 OCA], [http://www.ebi.ac.uk/pdbsum/2f41 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2f41 RCSB]</span> | ||
}} | }} | ||
| Line 27: | Line 30: | ||
[[Category: hot-dog fold]] | [[Category: hot-dog fold]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 02:57:40 2008'' |
Revision as of 23:57, 30 March 2008
| |||||||
| , resolution 2.50Å | |||||||
|---|---|---|---|---|---|---|---|
| Gene: | fapR (Bacillus subtilis) | ||||||
| Related: | 2F3X
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| 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
Page seeded by OCA on Mon Mar 31 02:57:40 2008
