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
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.