Chemistry Reference
In-Depth Information
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
2þ
, both linear and trigonal geometries are present in Hg
2þ
complexes and proteins
such as the Hg
2þ
-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
2þ
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
2þ
and As
3þ
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
3þ
with a tripodal coordination sphere (Figure 1.19a). This As-peptide
complex mimics possible As
3þ
binding to the bacterial As-responsive repressor protein
ArsR which dissociates from DNA upon As
3þ
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
2þ
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
2þ
(at the L9Pen
site) and Zn
2þ
(at the L23H site) to fold into a triple-helical bundle structure
(Figure 1.19b) [249]. Therein the Zn
2þ
site is four-coordinate with one coordination site
occupied by a water molecule analogous to the catalytic Zn
2þ
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
2þ
(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
2þ
(1.6
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