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Title: d -Cysteine Ligands Control Metal Geometries within De Novo Designed Three-Stranded Coiled Coils

Authors:
 [1];  [2];  [3];  [4];  [5];  [3]
  1. Department of Chemistry, University of Michigan, Ann Arbor Michigan 48109 USA, Present address: Department Chemistry, Faculty of Science, King Mongkut's University of Technology Thonburi (KMUTT), Bang Mod, ThungKhru, Bangkok 10140 Thailand
  2. Department of Chemistry, University of Michigan, Ann Arbor Michigan 48109 USA, Present address: School of Chemistry, University of Birmingham, Edgbaston, Birmingham B15 2TT UK
  3. Department of Chemistry, University of Michigan, Ann Arbor Michigan 48109 USA
  4. Department of Chemistry, University of Copenhagen, Universitetsparken 5 2100 København Ø Denmark
  5. Life Sciences Institute, University of Michigan, Ann Arbor Michigan 48109 USA
Publication Date:
Sponsoring Org.:
USDOE
OSTI Identifier:
1401777
Grant/Contract Number:
AC02-06CH11357; 085P1000817
Resource Type:
Journal Article: Publisher's Accepted Manuscript
Journal Name:
Chemistry - A European Journal
Additional Journal Information:
Journal Volume: 23; Journal Issue: 34; Related Information: CHORUS Timestamp: 2017-10-20 17:38:41; Journal ID: ISSN 0947-6539
Publisher:
Wiley Blackwell (John Wiley & Sons)
Country of Publication:
Germany
Language:
English

Citation Formats

Ruckthong, Leela, Peacock, Anna F. A., Pascoe, Cherilyn E., Hemmingsen, Lars, Stuckey, Jeanne A., and Pecoraro, Vincent L. d -Cysteine Ligands Control Metal Geometries within De Novo Designed Three-Stranded Coiled Coils. Germany: N. p., 2017. Web. doi:10.1002/chem.201700660.
Ruckthong, Leela, Peacock, Anna F. A., Pascoe, Cherilyn E., Hemmingsen, Lars, Stuckey, Jeanne A., & Pecoraro, Vincent L. d -Cysteine Ligands Control Metal Geometries within De Novo Designed Three-Stranded Coiled Coils. Germany. doi:10.1002/chem.201700660.
Ruckthong, Leela, Peacock, Anna F. A., Pascoe, Cherilyn E., Hemmingsen, Lars, Stuckey, Jeanne A., and Pecoraro, Vincent L. Fri . "d -Cysteine Ligands Control Metal Geometries within De Novo Designed Three-Stranded Coiled Coils". Germany. doi:10.1002/chem.201700660.
@article{osti_1401777,
title = {d -Cysteine Ligands Control Metal Geometries within De Novo Designed Three-Stranded Coiled Coils},
author = {Ruckthong, Leela and Peacock, Anna F. A. and Pascoe, Cherilyn E. and Hemmingsen, Lars and Stuckey, Jeanne A. and Pecoraro, Vincent L.},
abstractNote = {},
doi = {10.1002/chem.201700660},
journal = {Chemistry - A European Journal},
number = 34,
volume = 23,
place = {Germany},
year = {Fri May 26 00:00:00 EDT 2017},
month = {Fri May 26 00:00:00 EDT 2017}
}

Journal Article:
Free Publicly Available Full Text
Publisher's Version of Record at 10.1002/chem.201700660

Citation Metrics:
Cited by: 1work
Citation information provided by
Web of Science

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  • Over the past two decades, designed metallopeptides have held the promise for understanding a variety of fundamental questions in metallobiochemistry; however, these dreams have not yet been realized because of a lack of structural data to elaborate the protein scaffolds before metal complexation and the resultant metalated structures which ultimately exist. This is because there are few reports of structural characterization of such systems either in their metalated or nonmetalated forms and no examples where an apo structure and the corresponding metalated peptide assembly have both been defined by X-ray crystallography. Herein we present X-ray structures of two de novomore » designed parallel three-stranded coiled coils (designed using the heptad repeat (a {yields} g)) CSL9C (CS = Coil Ser) and CSL19C in their nonmetalated forms, determined to 1.36 and 2.15 {angstrom} resolutions, respectively. Leucines from either position 9 (a site) or 19 (d site) are replaced by cysteine to generate the constructs CSL9C and CSL19C, respectively, yielding thiol-rich pockets at the hydrophobic interior of these peptides, suitable to bind heavy metals such as As(III), Hg(II), Cd(II), and Pb(II). We use these structures to understand the inherent structural differences between a and d sites to clarify the basis of the observed differential spectroscopic behavior of metal binding in these types of peptides. Cys side chains of (CSL9C){sub 3} show alternate conformations and are partially preorganized for metal binding, whereas cysteines in (CSL19C){sub 3} are present as a single conformer. Zn(II) ions, which do not coordinate or influence Cys residues at the designed metal sites but are essential for forming X-ray quality crystals, are bound to His and Glu residues at the crystal packing interfaces of both structures. These 'apo' structures are used to clarify the changes in metal site organization between metalated As(CSL9C){sub 3} and to speculate on the differential basis of Hg(II) binding in a versus d peptides. Thus, for the first time, one can establish general rules for heavy metal binding to Cys-rich sites in designed proteins which may provide insight for understanding how heavy metals bind to metallochaperones or metalloregulatory proteins.« less
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