Apoprotein Structure and Metal Binding Characterization of a de Novo Designed Peptide, α3DIV, that Sequesters Toxic Heavy Metals

Biochemistry
Jefferson S PlegariaVincent L Pecoraro

Abstract

De novo protein design is a biologically relevant approach that provides a novel process in elucidating protein folding and modeling the metal centers of metalloproteins in a completely unrelated or simplified fold. An integral step in de novo protein design is the establishment of a well-folded scaffold with one conformation, which is a fundamental characteristic of many native proteins. Here, we report the NMR solution structure of apo α3DIV at pH 7.0, a de novo designed three-helix bundle peptide containing a triscysteine motif (Cys18, Cys28, and Cys67) that binds toxic heavy metals. The structure comprises 1067 NOE restraints derived from multinuclear multidimensional NOESY, as well as 138 dihedral angles (ψ, φ, and χ1). The backbone and heavy atoms of the 20 lowest energy structures have a root mean square deviation from the mean structure of 0.79 (0.16) Å and 1.31 (0.15) Å, respectively. When compared to the parent structure α3D, the substitution of Leu residues to Cys enhanced the α-helical content of α3DIV while maintaining the same overall topology and fold. In addition, solution studies on the metalated species illustrated metal-induced stability. An increase in the melting temperatures was observed for Hg(II), Pb(II)...Continue Reading

References

Jan 1, 1975·Confinia Neurologica·G Dieckmann, R Hassler
Nov 20, 1991·Journal of Molecular Biology·D S WishartF M Richards
Jul 1, 1987·Proceedings of the National Academy of Sciences of the United States of America·A D FrankelC O Pabo
Aug 1, 1994·European Journal of Biochemistry·B G Malmström
Nov 1, 1995·Journal of Biomolecular NMR·F DelaglioA Bax
May 5, 1998·Folding & Design·J P SchneiderW F DeGrado
Jul 9, 1998·Protein Science : a Publication of the Protein Society·J W BrysonW F DeGrado
Nov 13, 1998·Proceedings of the National Academy of Sciences of the United States of America·M SalzmannK Wüthrich
Jan 15, 1999·Journal of Magnetic Resonance·M Rance Palmer AG3rd
Feb 3, 1999·Proceedings of the National Academy of Sciences of the United States of America·M SiedleckaA Bierzynski
May 13, 1999·Proceedings of the National Academy of Sciences of the United States of America·S T WalshW F DeGrado
Oct 21, 1999·Journal of Magnetic Resonance·J P LoriaA G Palmer
Jun 29, 2000·Annual Review of Biochemistry·W F DeGradoA Lombardi
Dec 23, 2000·Journal of Molecular Biology·S T WalshW F DeGrado
Apr 10, 2002·Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry·Laura S BusenlehnerDavid P Giedroc
Jul 4, 2002·Journal of the American Chemical Society·Manolis MatzapetakisVincent L Pecoraro
Feb 20, 2003·Protein Science : a Publication of the Protein Society·Scott T R WalshWilliam F DeGrado
Jun 26, 2003·Nucleic Acids Research·Leigh WillardDavid S Wishart
Dec 6, 2003·Proceedings of the National Academy of Sciences of the United States of America·Lidia CristianWilliam F DeGrado
Dec 13, 2003·Proceedings of the National Academy of Sciences of the United States of America·Yongjin ZhuFeng Gai
Aug 20, 2004·Methods in Molecular Biology·Peter Güntert
Feb 28, 2006·Journal of Cardiac Failure· Heart Failure Society Of America
Mar 29, 2006·Clinics in Laboratory Medicine·Danyal IbrahimDaniel E Rusyniak
Dec 23, 2006·Proteins·Aneerban BhattacharyaGaetano T Montelione
Jun 30, 2007·The Journal of Biological Chemistry·Lucia BanciNigel J Robinson
Jul 5, 2007·Proceedings of the National Academy of Sciences of the United States of America·Debra S TouwVincent L Pecoraro
Jul 20, 2007·Dalton Transactions : an International Journal of Inorganic Chemistry·David P Giedroc, Alphonse I Arunkumar
Sep 28, 2007·The Journal of Biological Chemistry·Jie QinBarry P Rosen
Oct 23, 2008·Proceedings of the National Academy of Sciences of the United States of America·Anna F A PeacockVincent L Pecoraro
Nov 26, 2008·Biochimica Et Biophysica Acta·David E Davidson, Bruce C Hill

❮ Previous
Next ❯

Citations

Oct 28, 2015·Metallomics : Integrated Biometal Science·Alison G TeboVincent L Pecoraro
Oct 3, 2015·Biochimica Et Biophysica Acta·Jefferson S PlegariaVincent L Pecoraro
Sep 19, 2015·Inorganic Chemistry·Jefferson S PlegariaVincent L Pecoraro
Aug 4, 2015·Accounts of Chemical Research·Catherine S Mocny, Vincent L Pecoraro
Jul 1, 2016·Protein Engineering, Design & Selection : PEDS·Sharon L GuffyBrian Kuhlman
May 18, 2017·Protein Science : a Publication of the Protein Society·William A Hansen, Sagar D Khare
Jul 4, 2018·Acta Crystallographica. Section D, Structural Biology·Thomas L EllinghausPaul D Adams
Nov 12, 2019·Chemistry : a European Journal·Emilie MathieuVincent Pecoraro
Aug 24, 2019·Angewandte Chemie·Tyler B J PinterVincent L Pecoraro
Sep 26, 2019·Frontiers in Molecular Biosciences·Marie HoarauE Neil G Marsh
Aug 31, 2018·Journal of the Royal Society, Interface·Katie J Grayson, J L Ross Anderson
Oct 20, 2017·ChemPhotoChem·Alison G TeboAlly Aukauloo
Sep 19, 2018·Inorganic Chemistry·Karl J KoebkeVincent L Pecoraro
Sep 7, 2021·Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry·Karl J KoebkeVincent L Pecoraro
Oct 16, 2021·Chemical Communications : Chem Comm·Ziyi WangPeng Zheng

❮ Previous
Next ❯

Related Concepts

Related Feeds

ApoE Phenotypes

Apolipoprotein E (APOE) is a protein involved in fat metabolism and associated with the pathogenesis of Alzheimer's disease and cardiovascular disease. Here is the latest research on APOE phenotypes.

Related Papers

Journal of the American Chemical Society
Gunnar T Dolphin
Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry
Chengmin QianWenxia Tang
© 2021 Meta ULC. All rights reserved