d-Cysteine Ligands Control Metal Geometries within De Novo Designed Three-Stranded Coiled Coils
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d-Cysteine Ligands Control Metal Geometries within De Novo Designed Three-Stranded Coiled Coils. / Ruckthong, Leela; Peacock, Anna F.A.; Pascoe, Cherilyn E.; Hemmingsen, Lars Bo Stegeager; Stuckey, Jeanne A.; Pecoraro, Vincent L.
I: Chemistry - A European Journal, Bind 23, Nr. 34, 2017, s. 8232-8243.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - d-Cysteine Ligands Control Metal Geometries within De Novo Designed Three-Stranded Coiled Coils
AU - Ruckthong, Leela
AU - Peacock, Anna F.A.
AU - Pascoe, Cherilyn E.
AU - Hemmingsen, Lars Bo Stegeager
AU - Stuckey, Jeanne A.
AU - Pecoraro, Vincent L.
PY - 2017
Y1 - 2017
N2 - Although metal ion binding to naturally occurring l-amino acid proteins is well documented, understanding the impact of the opposite chirality (d-)amino acids on the structure and stereochemistry of metals is in its infancy. We examine the effect of a d-configuration cysteine within a designed l-amino acid three-stranded coiled coil in order to enforce a precise coordination number on a metal center. The d chirality does not alter the native fold, but the side-chain re-orientation modifies the sterics of the metal binding pocket. l-Cys side chains within the coiled-coil structure have previously been shown to rotate substantially from their preferred positions in the apo structure to create a binding site for a tetra-coordinate metal ion. However, here we show by X-ray crystallography that d-Cys side chains are preorganized within a suitable geometry to bind such a ligand. This is confirmed by comparison of the structure of ZnIICl(CSL16DC)3 2- to the published structure of ZnII(H2O)(GRAND-CSL12AL16LC)3 -. Moreover, spectroscopic analysis indicates that the CdII geometry observed by using l-Cys ligands (a mixture of three- and four-coordinate CdII) is altered to a single four-coordinate species when d-Cys is present. This work opens a new avenue for the control of the metal site environment in man-made proteins, by simply altering the binding ligand with its mirror-imaged d configuration. Thus, the use of non-coded amino acids in the coordination sphere of a metal promises to be a powerful tool for controlling the properties of future metalloproteins.
AB - Although metal ion binding to naturally occurring l-amino acid proteins is well documented, understanding the impact of the opposite chirality (d-)amino acids on the structure and stereochemistry of metals is in its infancy. We examine the effect of a d-configuration cysteine within a designed l-amino acid three-stranded coiled coil in order to enforce a precise coordination number on a metal center. The d chirality does not alter the native fold, but the side-chain re-orientation modifies the sterics of the metal binding pocket. l-Cys side chains within the coiled-coil structure have previously been shown to rotate substantially from their preferred positions in the apo structure to create a binding site for a tetra-coordinate metal ion. However, here we show by X-ray crystallography that d-Cys side chains are preorganized within a suitable geometry to bind such a ligand. This is confirmed by comparison of the structure of ZnIICl(CSL16DC)3 2- to the published structure of ZnII(H2O)(GRAND-CSL12AL16LC)3 -. Moreover, spectroscopic analysis indicates that the CdII geometry observed by using l-Cys ligands (a mixture of three- and four-coordinate CdII) is altered to a single four-coordinate species when d-Cys is present. This work opens a new avenue for the control of the metal site environment in man-made proteins, by simply altering the binding ligand with its mirror-imaged d configuration. Thus, the use of non-coded amino acids in the coordination sphere of a metal promises to be a powerful tool for controlling the properties of future metalloproteins.
KW - Cadmium
KW - d-amino acids
KW - Protein design
KW - X-ray crystallography
KW - Zinc
U2 - 10.1002/chem.201700660
DO - 10.1002/chem.201700660
M3 - Journal article
C2 - 28384393
AN - SCOPUS:85019855642
VL - 23
SP - 8232
EP - 8243
JO - Chemistry: A European Journal
JF - Chemistry: A European Journal
SN - 0947-6539
IS - 34
ER -
ID: 179393311