Soft metal ions, Cd(II) and Hg (II), induce triple‐stranded α‐helical assembly and folding of a de novo designed peptide in their trigonal geometries

Li, Xiangqun; Suzuki, Kazuo; Kanaori, Kenji; Tajima, Kunihiko; Kashiwada, Ayumi; Hiroaki, Hidekazu; Kohda, Daisuke; Tanaka, Toshiki

doi:10.1110/ps.9.7.1327

Cited by 77 publications

(89 citation statements)

References 50 publications

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“…By 3 O species (574 ppm), differs from previously used [22,23] assignments for three-and four-coordinate Cd II and leads to the reassessment of earlier reports of pure three-coordinate Cd II . [4,23] The more challenging objective was to dehydrate the Cd II core environment.…”

Section: Figurementioning

confidence: 55%

“…[4,23] The more challenging objective was to dehydrate the Cd II core environment. We reasoned that if decreasing the substituent bulk above the metal site allowed the access of more water, and hence a higher metal-coordination number, then increasing the steric constraints might yield a less hydrated environment that could provide the desired adduct with a lower coordination number.…”

Section: Figurementioning

confidence: 99%

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Using Nonnatural Amino Acids to Control Metal‐Coordination Number in Three‐Stranded Coiled Coils

Lee

Cabello

Hemmingsen³

et al. 2006

Angew Chem Int Ed

108

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Section: Figurementioning

confidence: 55%

Section: Figurementioning

confidence: 99%

Using Nonnatural Amino Acids to Control Metal‐Coordination Number in Three‐Stranded Coiled Coils

Lee

Cabello

Hemmingsen³

et al. 2006

Angew Chem Int Ed

108

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“…The substantial research incorporating metal cofactors into designed peptide frameworks has been described in several recent reviews (13-15). Helical scaffolds have been the predominant structural motif used for the incorporation of many types of metal-binding sites, including hemes (16), iron-sulfur clusters (17), dinuclear metal centers (18), copper centers (19,20), and heavy metal-binding trigonal thiolate sites (7,21). ␤-Hairpins and other globular structures that bind As(III), Zn(II), and other metal cofactors have also been designed (22)(23)(24)(25).…”

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confidence: 99%

Identifying important structural characteristics of arsenic resistance proteins by using designed three-stranded coiled coils

Touw

Nordman

Stuckey³

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

155

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Arsenic, a contaminant of water supplies worldwide, is one of the most toxic inorganic ions. Despite arsenic's health impact, there is relatively little structural detail known about its interactions with proteins. Bacteria such as Escherichia coli have evolved arsenic resistance using the Ars operon that is regulated by ArsR, a repressor protein that dissociates from DNA when As(III) binds. This protein undergoes a critical conformational change upon binding As(III) with three cysteine residues. Unfortunately, structures of ArsR with or without As(III) have not been reported. Alternatively, de novo designed peptides can bind As(III) in an endo configuration within a thiolate-rich environment consistent with that proposed for both ArsR and ArsD. We report the structure of the As(III) complex of Coil Ser L9C to a 1.8-Å resolution, providing x-ray characterization of As(III) in a Tris thiolate protein environment and allowing a structural basis by which to understand arsenated ArsR.arsenic-binding proteins ͉ coiled coil peptides ͉ crystallography ͉ heavy metal toxicity ͉ protein design A rsenic toxicity is a worldwide problem as a natural contaminant of water supplies. Despite the fact that it is a human toxin and carcinogen, few structural reports on its interaction with biological ligands have appeared. Escherichia coli and other bacteria have evolved a detoxification mechanism that employs the arsRDABC operon (1). Arsenic removal by these encoded proteins is initiated when As(III) binds to ArsR, resulting in the dissociation of the repressor protein from the promoter DNA. The structure of the ArsA component of the ATP-dependent extrusion pump ArsAB with antimonite bound in close proximity to the nucleotide-binding site was able to provide some insight into the active transport of As(III) out of the cell (2). Additionally, structural characterization of substrate and product complexes of the arsenate reductase ArsC, which reduces arsenate (AsO 4 3Ϫ ) to arsenite (AsO 2 Ϫ ), has helped elucidate this step of the arsenic detoxification pathway (3, 4). Recent studies of E. coli ArsD indicate that it is a metallochaperone, transporting As(III) to ArsA for extrusion (5). Extended x-ray absorption fine structure and mutagenesis studies have shown that ArsR coordinates As(III) with three cysteine thiolates at a distance of 2.25 Å, a coordination mode that ArsD is also proposed to employ (1, 5). However, no x-ray or NMR structures of ArsR, the repressor protein, or ArsD have been reported to date. Furthermore, AsS 3 structures have not been reported for any biologically relevant small-molecule thiolates, such as glutathione, and only a handful of related AsS 3 complexes with aromatic ligands or chelated alkyl dithiolate coordination are reported (6).We set out to model the putative As(III) coordination environments of ArsR and ArsD in a designed peptide system. Previously, we have shown that the three-stranded coiled coildesigned with the heptad repeat strategy, such as TRI L16C (sequences of all peptides are in Table 1...

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“…Examples where the metals are bound in ligation environments that are not thermodynamically favored in the absence of the polypeptide backbone are uncommon. However, recent designs of de novo proteins containing Hg(SR) 3 Ϫ centers (7,28), dimeric metallocenters (29,30), iron-sulfur clusters (31), Ni-X-Fe 4 S 4 centers (32,33), and hemes with open coordination sites (34) demonstrate that the design of complex metal centers where the ultimate structure of the metalloprotein is determined by an interplay of polypeptide backbone and metal coordination stabilities is feasible. A fundamental understanding of the formation of these metal centers is essential to facilitate the successful design of functional metalloproteins.…”

Section: Discussionmentioning

confidence: 99%

Hg(II) binding to a weakly associated coiled coil nucleates an encoded metalloprotein fold: A kinetic analysis

Farrer

Pecoraro

2003

Proc. Natl. Acad. Sci. U.S.A.

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A detailed kinetic analysis of metal encapsulation by a de novodesigned protein is described. The kinetic mechanism of Hg(II) encapsulation in the three-stranded coiled coil formed by the peptide CH 3CO Metalloproteins are ubiquitous throughout nature. In metalloproteins, the metal site is necessary for proper function through either stabilization of the overall structure or direct involvement in the active center of the protein. Design of metalloproteins is concerned with the structure of the polypeptide backbone, the coordination environment around the metal, and how the forces governing both interact to generate the overall structure of the metalloprotein.An integral part of understanding the overall structure of a metalloprotein is to understand how, in time, the metalloprotein achieves its overall structure. Current research on natural protein systems has yielded information that both the metal and the structure of the polypeptide backbone play key roles in the folding processes for many proteins. Demonstrating the importance of metal coordination, the folding of ferricytochrome c from its chemically denatured form occurs through a multistep process where the metal coordination environment plays a pivotal role in determining the kinetic profile (1, 2). Highlighting the role of the polypeptide backbone, the addition of Cu(II) to azurin has been shown to occur faster in the unfolded apoenzyme than to the structured apo enzyme (3-6).We have been investigating designed peptides that bind heavy metals. This family of peptides is based on the parent peptide CH 3 CO-G(LKALEEK) 4 G-NH 2 (TRI) (7,8). We intend to elucidate the structures and properties of heavy metal-protein interactions and to reveal the protein forces involved in controlling coordination environments around metal centers. At high pH (pH Ͼ 7.0), TRI assembles into a three-stranded coiled coil with a leucine core. By replacing one of the leucines with cysteine on each peptide strand, a metal-binding site presenting a trigonal thiol͞thiolate environment to a metal is created. We reported trigonal thiolate complexation of As(III

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Soft metal ions, Cd(II) and Hg (II), induce triple‐stranded α‐helical assembly and folding of a de novo designed peptide in their trigonal geometries

Cited by 77 publications

References 50 publications

Using Nonnatural Amino Acids to Control Metal‐Coordination Number in Three‐Stranded Coiled Coils

Using Nonnatural Amino Acids to Control Metal‐Coordination Number in Three‐Stranded Coiled Coils

Identifying important structural characteristics of arsenic resistance proteins by using designed three-stranded coiled coils

Hg(II) binding to a weakly associated coiled coil nucleates an encoded metalloprotein fold: A kinetic analysis

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