Using diastereopeptides to control metal ion coordination in proteins

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Using diastereopeptides to control metal ion coordination in proteins. / Peacock, Anna; Hemmingsen, L; Pecoraro, VL.

In: National Academy of Sciences. Proceedings, Vol. 105, No. 43, 28.10.2008, p. 16566-16571.

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Peacock, Anna ; Hemmingsen, L ; Pecoraro, VL. / Using diastereopeptides to control metal ion coordination in proteins. In: National Academy of Sciences. Proceedings. 2008 ; Vol. 105, No. 43. pp. 16566-16571.

Bibtex

@article{da81ec85f8e94805b912497d40db912c,
title = "Using diastereopeptides to control metal ion coordination in proteins",
abstract = "Here, we report a previously undescribed approach for controlling metal ion coordination geometry in biomolecules by reorientating amino acid side chains through substitution of L- to D-amino acids. These diastereopeptides allow us to manipulate the spatial orientation of amino acid side chains to alter the sterics of metal binding pockets. We have used this approach to design the de novo metallopeptide, Cd(TRIL12L(D)L16C)(3)(-), which is an example of Cd(II) bound to 3 L-Cys as exclusively trigonal CdS3, as characterized by a combination of Cd-113 NMR and Cd-111m PAC spectroscopy. We subsequently show that the physical properties of such a site, such as the high pK(a2) for Cd(II) binding of 15.1, is due to the nature of the coordination number and not the ligating group. Furthermore this approach allowed for the design of a construct, GRANDL12L(D)L16CL26AL30C, capable of independently binding 2 equivalents of Cd(II) to 2 very similar Cys sites as exclusively 3- and 4-, CdS3 and CdS3O, respectively. Demonstrating that we are capable of controlling the Cd(II) coordination number in these 2 sites solely by varying the nature of a noncoordinating second coordination sphere amino acid, with D-leucine and L-alanine resulting in exclusively 3- and 4-coordinate structures, respectively. Cd(II) was found to selectively bind to the 4-coordinate CdS3O site, demonstrating that a protein can be designed that displays metalbinding selectivity based solely on coordination number control and not on the chemical identity of coordinating ligands.",
keywords = "de novo metallopeptide design, coiled-coil peptides, cadmium, D-amino acids",
author = "Anna Peacock and L Hemmingsen and VL Pecoraro",
year = "2008",
month = "10",
day = "28",
doi = "10.1073/pnas.0806792105",
language = "English",
volume = "105",
pages = "16566--16571",
journal = "National Academy of Sciences. Proceedings",
issn = "1091-6490",
publisher = "National Academy of Sciences",
number = "43",

}

RIS

TY - JOUR

T1 - Using diastereopeptides to control metal ion coordination in proteins

AU - Peacock, Anna

AU - Hemmingsen, L

AU - Pecoraro, VL

PY - 2008/10/28

Y1 - 2008/10/28

N2 - Here, we report a previously undescribed approach for controlling metal ion coordination geometry in biomolecules by reorientating amino acid side chains through substitution of L- to D-amino acids. These diastereopeptides allow us to manipulate the spatial orientation of amino acid side chains to alter the sterics of metal binding pockets. We have used this approach to design the de novo metallopeptide, Cd(TRIL12L(D)L16C)(3)(-), which is an example of Cd(II) bound to 3 L-Cys as exclusively trigonal CdS3, as characterized by a combination of Cd-113 NMR and Cd-111m PAC spectroscopy. We subsequently show that the physical properties of such a site, such as the high pK(a2) for Cd(II) binding of 15.1, is due to the nature of the coordination number and not the ligating group. Furthermore this approach allowed for the design of a construct, GRANDL12L(D)L16CL26AL30C, capable of independently binding 2 equivalents of Cd(II) to 2 very similar Cys sites as exclusively 3- and 4-, CdS3 and CdS3O, respectively. Demonstrating that we are capable of controlling the Cd(II) coordination number in these 2 sites solely by varying the nature of a noncoordinating second coordination sphere amino acid, with D-leucine and L-alanine resulting in exclusively 3- and 4-coordinate structures, respectively. Cd(II) was found to selectively bind to the 4-coordinate CdS3O site, demonstrating that a protein can be designed that displays metalbinding selectivity based solely on coordination number control and not on the chemical identity of coordinating ligands.

AB - Here, we report a previously undescribed approach for controlling metal ion coordination geometry in biomolecules by reorientating amino acid side chains through substitution of L- to D-amino acids. These diastereopeptides allow us to manipulate the spatial orientation of amino acid side chains to alter the sterics of metal binding pockets. We have used this approach to design the de novo metallopeptide, Cd(TRIL12L(D)L16C)(3)(-), which is an example of Cd(II) bound to 3 L-Cys as exclusively trigonal CdS3, as characterized by a combination of Cd-113 NMR and Cd-111m PAC spectroscopy. We subsequently show that the physical properties of such a site, such as the high pK(a2) for Cd(II) binding of 15.1, is due to the nature of the coordination number and not the ligating group. Furthermore this approach allowed for the design of a construct, GRANDL12L(D)L16CL26AL30C, capable of independently binding 2 equivalents of Cd(II) to 2 very similar Cys sites as exclusively 3- and 4-, CdS3 and CdS3O, respectively. Demonstrating that we are capable of controlling the Cd(II) coordination number in these 2 sites solely by varying the nature of a noncoordinating second coordination sphere amino acid, with D-leucine and L-alanine resulting in exclusively 3- and 4-coordinate structures, respectively. Cd(II) was found to selectively bind to the 4-coordinate CdS3O site, demonstrating that a protein can be designed that displays metalbinding selectivity based solely on coordination number control and not on the chemical identity of coordinating ligands.

KW - de novo metallopeptide design

KW - coiled-coil peptides

KW - cadmium

KW - D-amino acids

U2 - 10.1073/pnas.0806792105

DO - 10.1073/pnas.0806792105

M3 - Article

C2 - 18940928

VL - 105

SP - 16566

EP - 16571

JO - National Academy of Sciences. Proceedings

JF - National Academy of Sciences. Proceedings

SN - 1091-6490

IS - 43

ER -