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Figure 1.10 Left: the tight G12-P13-b-turn in Cu,Zn-superoxide dismutase (PDB ID 1QE).
Right: the metal-binding P86 turn in plastocyanin (PDB ID 1AG6).
and synthesis of a b-turn mimetic library targeting the major recognition motifs in protein-
protein and peptide-receptor interactions [74].
1.3.1 Antibiotic Metallopeptides
There are many antibiotic peptides of diverse structures isolated from various sources
which interact with a variety of biomolecules, resulting in the inhibition of the associated
biochemical or biophysical processes which frequently are associated with conforma-
tional changes of the peptides and/or the targets. A number of antibiotics need metal ions
to function properly, thus dubbed “metalloantibiotics” [75], such as the peptide bacitracin
(Bc) from
Bacillus
species [76] and the peptides/ketide bleomycin (Blm) from the culture
medium of
Streptomyces verticullus
[77]. Metal binding to these antibiotics results in
significant conformational changes, such as the
180
twisting of the simple antibiotic
streptonigrin upon metal binding [78,79]. A few prototypical antibiotic metallopeptides
are discussed in this section to show conformational changes of these peptides associated
with metal binding and interaction with targets.
1.3.1.1 Metallo-Blm and DNA Binding
Blm is a Cu
2þ
-containing glycopeptidyl antibiotic excreted by
Streptomyces verticullus
[80,81] which also exhibits antiviral [82] and anticancer [83] activities and is widely used
in chemotherapy. Blm contains a few uncommon amino acids, that is, b-amino-Ala,
b-hydroxy-His, and methylvalerate and a peptidyl bithiazole chain for DNA binding (
1
,
with potential metal-binding sites marked in red). It is the most extensively studied metal-
loantibiotic from various view points [75], including structures, oxidative DNA cleavage,
and use as a model system to gain further insights into O
2
activation by nonheme Fe
enzyme [84]. DNA cleavage by Fe-Blm is carried out by the active O
Fe
V/IV
-Blm spe-
cies via oxidation at C4
0
and C2
0
-H proton abstraction immediately after the 5
0
GC and
5
0
GT sequences [84-87], Fe
2þ
-Blm can also bind and cleave RNA molecules [88],
including tRNA and its precursors and rRNA [89] mainly at the junctions between dou-
ble- and single-stranded regions [90], and also DNA-RNA hybrids [8b,[91]].
¼
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