Metalloproteins and Metallopeptides –Natural Metallofoldamers - Metallofoldamers: Supramolecular Architectures from Helicates to Biomimetics - page 20

Figure 1.14 Bottom: stereoview of the crystal structure of FhuA with a bound Fe 3þ -ferri-
chrome complex PDB 1FCP. The structure of the receptor with a bound Fe-albomycin com-
plex is similar (PDB 1QKC). Top: detailed view of the complex.
uptake A protein) with and without a bound Fe 3þ -siderophore have been determined (Fig-
ure 1.14, bottom) [179]. Some Fe 3þ -siderophore complexes have quite similar folding
and coordination chemistry upon their binding to FhuA. The binding of Fe 3þ -ferrichrome
(comprised of Gly and ornithine hydroximate; Figure 1.14, top) to FhuA induces a signifi-
cant conformational change at the N-terminal domain of the receptor. However, the stud-
ies could not identify how the conformational change results in the uptake and transport
of the complexes through the cell membrane.
1.3.2 Metallopeptides in Neurodegenerative Diseases
Protein misfolding, self-assembling, and/or aggregation can be associated with neuro-
degenerative diseases, such as the Cu,Zn-superoxide dismutase and amyotrophic lateral
sclerosis discussed above, the abnormal aggregation and accumulation of a-synuclein in
Parkinson's disease, aggregation-prone mutant huntingtin in Huntington's disease, and
the aggregation of prion protein in a few types of transmissible spongiform encephalopa-
thies. In this section, the conformation and metal binding of two prototypical metallopep-
tides/proteins associated with neurodegenerative diseases are discussed: b-amyloid and
prion, as well as their fragments.