Crystal structure of FadR, a fatty acid-responsive transcription factor with a novel acyl coenzyme A-binding fold

Citation
Dmf. Van Aalten et al., Crystal structure of FadR, a fatty acid-responsive transcription factor with a novel acyl coenzyme A-binding fold, EMBO J, 19(19), 2000, pp. 5167-5177
Citations number
53
Categorie Soggetti
Molecular Biology & Genetics
Journal title
EMBO JOURNAL
ISSN journal
02614189 → ACNP
Volume
19
Issue
19
Year of publication
2000
Pages
5167 - 5177
Database
ISI
SICI code
0261-4189(20001002)19:19<5167:CSOFAF>2.0.ZU;2-P
Abstract
FadR is a dimeric acyl coenzyme A (acyl CoA)-binding protein and transcript ion factor that regulates the expression of genes encoding fatty acid biosy nthetic and degrading enzymes in Escherichia coli, Here, the 2.0 Angstrom c rystal structure of full-length FadR is described, determined using multi-w avelength anomalous dispersion, The structure reveals a dimer and a two-dom ain fold, with DNA-binding and acyl-CoA-binding sites located in an N-termi nal and C-terminal domain, respectively, The N-terminal domain contains a w inged helix-turn-helix prokaryotic DNA-binding fold, Comparison with known structures and analysis of mutagenesis data delineated the site of interact ion with DNA, The C-terminal domain has a novel fold, consisting of a seven -helical bundle with a crossover topology, Careful analysis of the structur e, together with mutational and biophysical data, revealed a putative hydro phobic acyl-CoA-binding site, buried in the core of the seven-helical bundl e. This structure aids in understanding FadR function at a molecular level, provides the first structural scaffold for the large GntR family of transc ription factors, which are keys in the control of metabolism in bacterial p athogens, and could thus be a possible target for novel chemotherapeutic ag ents.