Structural characterization of a ligand-bound form of Bacillus subtilis FadR involved in the regulation of fatty acid degradation

Proteins
Masahiro FujihashiKunio Miki

Abstract

Bacillus subtilis FadR (FadR(Bs)), a member of the TetR family of bacterial transcriptional regulators, represses five fad operons including 15 genes, most of which are involved in β-oxidation of fatty acids. FadR(Bs) binds to the five FadR(Bs) boxes in the promoter regions and the binding is specifically inhibited by long-chain (C14-C20 ) acyl-CoAs, causing derepression of the fad operons. To elucidate the structural mechanism of this regulator, we have determined the crystal structures of FadR(Bs) proteins prepared with and without stearoyl(C18)-CoA. The crystal structure without adding any ligand molecules unexpectedly includes one small molecule, probably dodecyl(C12)-CoA derived from the Escherichia coli host, in its homodimeric structure. Also, we successfully obtained the structure of the ligand-bound form of the FadR(Bs) dimer by co-crystallization, in which two stearoyl-CoA molecules are accommodated, with the binding mode being essentially equivalent to that of dodecyl-CoA. Although the acyl-chain-binding cavity of FadR(Bs) is mainly hydrophobic, a hydrophilic patch encompasses the C1-C10 carbons of the acyl chain. This accounts for the previous report that the DNA binding of FadR(Bs) is specifically inhibited by the ...Continue Reading

References

Oct 10, 1998·Molecular Microbiology·J E Cronan, S Subrahmanyam
Mar 25, 1999·Acta Crystallographica. Section D, Biological Crystallography·G N MurshudovE J Dodson
Sep 22, 2001·Acta Crystallographica. Section D, Biological Crystallography·A A Vagin, M N Isupov
Dec 12, 2001·Science·M A SchumacherR G Brennan
Feb 23, 2002·The Journal of Biological Chemistry·Yong-Mei ZhangCharles O Rock
May 10, 2003·Developmental Cell·Gustavo E SchujmanDiego de Mendoza
Jul 17, 2004·The EMBO Journal·Maria A SchumacherRichard G Brennan
Sep 1, 1994·Acta Crystallographica. Section D, Biological Crystallography·UNKNOWN Collaborative Computational Project, Number 4
Jul 1, 1996·Acta Crystallographica. Section D, Biological Crystallography·G J Kleywegt
Jun 10, 2005·Microbiology and Molecular Biology Reviews : MMBR·Juan L RamosRaquel Tobes
Dec 19, 2006·Methods in Molecular Biology·Gerard J Kleywegt
Dec 26, 2006·The Journal of Biological Chemistry·Hiroshi MatsuokaYasutaro Fujita
May 1, 2007·Journal of Molecular Biology·Yilmaz AlguelXiaodong Zhang
Sep 20, 2007·Molecular Microbiology·Yong-Mei ZhangCharles O Rock
Oct 9, 2007·Molecular Microbiology·Yasutaro FujitaKazutake Hirooka
Oct 13, 2009·Journal of Bacteriology·Marco BellinzoniPedro M Alzari
Jan 9, 2010·Acta Crystallographica. Section D, Biological Crystallography·Vincent B ChenDavid C Richardson
Apr 13, 2010·Acta Crystallographica. Section D, Biological Crystallography·P EmsleyK Cowtan
Jul 20, 2010·Nature Structural & Molecular Biology·Darcie J MillerStephen W White
Aug 8, 2012·Acta Crystallographica. Section F, Structural Biology and Crystallization Communications·Young Woo ParkJae Young Lee
Jan 1, 1997·Methods in Enzymology·Zbyszek Otwinowski, Wladek Minor

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Citations

May 20, 2015·International Journal of Food Microbiology·Sara Esther DiomandéJulien Brillard
Aug 25, 2015·Frontiers in Microbiology·Sara E DiomandéJulien Brillard
Mar 22, 2015·The Journal of Biological Chemistry·Javier F JuárezEduardo Díaz
Jun 6, 2017·Frontiers in Microbiology·Dominik TödterJörg Stülke
Nov 20, 2014·The Journal of Biological Chemistry·Adam M CroweLindsay D Eltis
Jan 11, 2021·Molecular Biotechnology·Dipanwita MaityAmitava Bandhu

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