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Figure 1.18 A dimeric four-helical bundle peptide with a dinuclear metal center, repre-
sented herein by the di-Zn form solved with NMR (PDB 2KIK). The crystal structure of this
helical bundle metallopeptide has a similar structure (PDB 1EC5). The peptide folding is
shown in a stereo view with the image on the right also showing the molecular surface and
Gly9 labeled in red.
conformational change differently: Ni induced the formation of a helical structure, but
not Cu [233].
The role of metal ions has further been demonstrated in assisting peptides to adopt a
specific conformation and then assemble into a certain tertiary or quaternary structure,
such as the helical bundles [234] found in many metalloproteins, including cytochrome c
(Figure 1.2). A designed helical bundle-forming metallopeptide demonstrates that hydro-
phobic interactions are sufficient to induce polypeptide folding, while the introduction of
metal-binding sites can further “tighten up” a four-bundle helical structure [235]. Therein,
the four-helix bundle is formed as a dimer of helix-turn-helix peptides and two Zn -
binding sites are built in to form a dinuclear center (Figure 1.18) [236]. An overall C 2 -
rotation symmetry of the dimer and the dinuclear metal sites is revealed from the crystal
structure. The metal binding sites in this dimeric peptide and a few variants [237] can also
accommodate various dinuclear metal centers with an overall folding and assembly analo-
gous to the di-Zn peptide with some variations in the coordination sphere of the metal-
binding site [238]. The variant L9G/L13G has a larger opening to the dimetal site than
the original peptide, affording substrate accessibility and significant oxidation activities
for the di-Fe complex, with k cat / K m ¼
105M 1 s 1 for the oxidation of 3,5-dimethylcate-
chol and 23M 1 s 1 for 4-aminophenol oxidation [23b].
In addition to metal binding to the helical bundles, the prosthetic group metal-porphyrin
can also be incorporated into peptides and assist the folding of the peptides and in some cases
render catalysis possible. A designed peptide containing two His residues can be folded and
assembled into a tetrameric helical bundle upon binding two Fe(III)-porphyrin molecules,
with each one coordinated to two peptide chains via two His residues [239]. Moreover, a
heterodimeric peptide with a protophorphyrin IV covalently linked to two peptide chains
folds mainly to a helical structure. Here the heme-Fe is five-coordinate via binding to one
His from one peptide chain, leaving an open site for possible substrate and/or peroxide bind-
ing, as in the case of heme-containing peroxidases. This heme-peptide complex indeed
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