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Figure 1.19 Stereo views of the crystal structures of (a) As(L9C) 3 (PDB 2JGO) and (b) Zn,Hg
(Leu9Pen/ Leu23His) 3 . The metal-binding sites are shown as spheres (As, red; Hg, gray; Zn,
green).
shows a significant peroxidase activity toward 2,2 0 -azino-di(3-ethyl-benzothiazoline-6-
sulfonic acid (ABTS; k cat / K m ¼
4417M 1 s 1 ) and 2-methoxyphenol (870mM 1 s 1 ) [240].
Metal ions have characteristic coordination geometries, such as the presence of bridg-
ing carboxylate and hydroxide/oxide in di-Fe centers, as illustrated above. In the case of
Hg , both linear and trigonal geometries are present in Hg complexes and proteins
such as the Hg -detoxification regulatory factor MerR [241]. The peptide Ac-G(LKA-
LEEK) 4 G-CONH 2 forms triple-helical bundles [242] which can be further modified with
Cys at position 12 or 16 to afford mutants L12C or L16C that bind Hg in a pH-depen-
dent manner [243], that is, a linear geometry as Hg(L12C) 2 at low pH and a trigonal pla-
nar coordination sphere as Hg(L12C) 3 at high pH [244] and as Hg(L16C) 2 at low L16C
concentrations and Hg(L16C) 3 at high peptide concentrations at pH 8.5 [245]. These Cys-
containing peptides also bind Cd and As to fold into triple-helical bundles [244,246].
The crystal structure of the complex As(L9C) 3 reveals parallel helical bundles and Cys-
coordinated As with a tripodal coordination sphere (Figure 1.19a). This As-peptide
complex mimics possible As binding to the bacterial As-responsive repressor protein
ArsR which dissociates from DNA upon As binding as the regulatory control in bacte-
rial arsenic resistance [247].
Further metal-binding properties of the peptide were pursued by the use of a double
mutant L9C/L19C which binds two Cd ions sequentially, the Cys-9 site first followed
by the Cys-19 site, to form a triple-helical bundle structure [248]. An analogous sulfur-
and His-containing peptide L9PenL23H (Pen
penicillamine) with the sequence Ac-E
WEALEKK (Pen)AALESK LQALEKK HEALEHG-NH 2 binds both Hg (at the L9Pen
site) and Zn (at the L23H site) to fold into a triple-helical bundle structure
(Figure 1.19b) [249]. Therein the Zn site is four-coordinate with one coordination site
occupied by a water molecule analogous to the catalytic Zn site in carbonic anhydrase,
rendering hydrolytic/hydration catalysis possible by this mixed-metal metallopeptide. In a
different case, a much longer designed peptide of 73 amino acids is folded by Zn
(2.5
¼
10 5 M) into a four-helical bundle structure with two
metal-binding Cys-x-x-x-His sequences on adjacent helices, wherein a tetrahedral N 2 S 2
10 8 M) or Co (1.6
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