De novo design of a D2-symmetrical protein that reproduces the diheme four-helix bundle in cytochrome bc1

Journal of the American Chemical Society
Giovanna GhirlandaWilliam F DeGrado

Abstract

An idealized, water-soluble D(2)-symmetric diheme protein is constructed based on a mathematical parametrization of the backbone coordinates of the transmembrane diheme four-helix bundle in cytochrome bc(1). Each heme is coordinated by two His residues from diagonally apposed helices. In the model, the imidazole rings of the His ligands are held in a somewhat unusual perpendicular orientation as found in cytochrome bc(1), which is maintained by a second-shell hydrogen bond to a Thr side chain on a neighboring helix. The resulting peptide is unfolded in the apo state but assembles cooperatively upon binding to heme into a well-folded tetramer. Each tetramer binds two hemes with high affinity at low micromolar concentrations. The equilibrium reduction midpoint potential varies between -76 mV and -124 mV vs SHE in the reducing and oxidizing direction, respectively. The EPR spectrum of the ferric complex indicates the presence of a low-spin species, with a g(max) value of 3.35 comparable to those obtained for hemes b of cytochrome bc(1) (3.79 and 3.44). This provides strong support for the designed perpendicular orientation of the imidazole ligands. Moreover, NMR spectra show that the protein exists in solution in a unique conforma...Continue Reading

References

Feb 15, 1987·Analytical Biochemistry·E A Berry, B L Trumpower
Mar 31, 1994·Nature·D E RobertsonP L Dutton
Sep 1, 1995·Journal of Biomolecular NMR·D S WishartB D Sykes
Oct 6, 1997·Science·B I Dahiyat, S L Mayo
Jul 29, 1998·Journal of Biomolecular NMR·J J SkalickyA J Wand
Sep 8, 1998·Current Opinion in Structural Biology·J R Desjarlais, N D Clarke
Nov 20, 1998·Science·P B HarburyP S Kim
Jun 23, 1999·Structure·A G Street, S L Mayo
Jul 2, 1999·Journal of Molecular Biology·J R Desjarlais, T M Handel
Jan 2, 2001·Bioorganic & Medicinal Chemistry Letters·I ObatayaH Mihara
Jan 12, 2001·Inorganic Chemistry·D L Huffman, K S Suslick
Jun 30, 2001·Journal of Biomolecular NMR·J MarleyC Bracken
Aug 29, 2001·Biochemistry·B R GibneyP L Dutton
Sep 5, 2001·Journal of Molecular Biology·B NorthW F DeGrado
Nov 17, 2001·Chemical Reviews·D A Moffet, M H Hecht
Sep 11, 2002·Journal of Molecular Biology·Christopher M SummaWilliam F DeGrado
Oct 17, 2002·Journal of the American Chemical Society·Michael M RosenblattKenneth S Suslick
Feb 19, 2003·Journal of Molecular Biology·Steve S HuangMitchell Lewis
Aug 5, 2003·Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry·Rüdiger BendaF Ann Walker

❮ Previous
Next ❯

Citations

Apr 7, 2005·Current Opinion in Chemical Biology·Debdip Ghosh, Vincent L Pecoraro
Jun 14, 2005·Journal of Molecular Biology·Alexander ProdöhlDirk Schneider
Aug 19, 2007·Journal of the American Chemical Society·Gretchen M BenderWilliam F DeGrado
Jan 1, 2009·Faraday Discussions·Craig T ArmstrongDerek N Woolfson
Feb 7, 2012·Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry·Sandip ShindeGiovanna Ghirlanda
Dec 18, 2015·Biochimica Et Biophysica Acta·Geetha GoparajuBohdana M Discher
Jul 19, 2008·Proteins·Christopher NegronRonald L Koder
Oct 10, 2015·Biochimica Et Biophysica Acta·Vikas NandaDror Noy
May 16, 2017·Journal of the American Chemical Society·Lee A SolomonH Christopher Fry
Nov 24, 2017·Nature Chemistry·Nicholas F PolizziWilliam F DeGrado
Jun 21, 2006·Dalton Transactions : an International Journal of Inorganic Chemistry·Ronald L Koder, P Leslie Dutton
Mar 14, 2007·Biopolymers·Jon O FreemanJohn C Sherman
Oct 31, 2008·Organic & Biomolecular Chemistry·Vincent DuléryTamis Darbre
Apr 23, 2010·Chemphyschem : a European Journal of Chemical Physics and Physical Chemistry·Ana P Gámiz-HernándezErnst-Walter Knapp
Jun 15, 2010·Proteins·Lorna J SmithJanet M Thornton
Feb 24, 2011·Angewandte Chemie·Saumen ChakrabortyVincent L Pecoraro
Nov 15, 2012·Chemistry : a European Journal·Marina FaiellaVincenzo Pavone
Dec 20, 2019·ELife·Jooyoung ParkDavid Baker
Feb 3, 2021·The Journal of Physical Chemistry. B·H Christopher FryAndrew L Ferguson
Oct 5, 2013·Biochemistry·Anindya RoyGiovanna Ghirlanda
Mar 26, 2014·Chemical Reviews·Fangting YuVincent L Pecoraro
Oct 11, 2017·Journal of the American Chemical Society·Woon Ju SongF Akif Tezcan
Mar 31, 2005·Journal of the American Chemical Society·Julien Bachmann, Daniel G Nocera
Oct 30, 2007·Journal of the American Chemical Society·Jiangyun WangKenneth S Suslick
Jan 18, 2007·Journal of the American Chemical Society·Jeanine M CordovaGiovanna Ghirlanda
May 18, 2006·Journal of the American Chemical Society·Joe SwiftIvan J Dmochowski
Dec 8, 2005·Biochemistry·Barbara SpolaoreAngelo Fontana
Feb 3, 2005·Journal of the American Chemical Society·Frank V CochranWilliam F DeGrado

❮ Previous
Next ❯

Related Concepts

Related Feeds

Bacterial Respiration

This feed focuses on cellular respiration in bacteria, known as bacterial respiration. Discover the latest research here.