2 research outputs found
Model Peptide Studies Reveal a Mixed Histidine-Methionine Cu(I) Binding Site at the NāTerminus of Human Copper Transporter 1
Copper
is a vital metal cofactor in enzymes that are essential to myriad
biological processes. Cellular acquisition of copper is primarily
accomplished through the Ctr family of plasma membrane copper transport
proteins. Model peptide studies indicate that the human Ctr1 N-terminus
binds to CuĀ(II) with high affinity through an amino terminal CuĀ(II),
NiĀ(II) (ATCUN) binding site. Unlike typical ATCUN-type peptides, the
Ctr1 peptide facilitates the ascorbate-dependent reduction of CuĀ(II)
bound in its ATCUN site by virtue of an adjacent HH (<i>bis</i>-His) sequence in the peptide. It is likely that the CuĀ(I) coordination
environment influences the redox behavior of Cu bound to this peptide;
however, the identity and coordination geometry of the CuĀ(I) site
has not been elucidated from previous work. Here, we show data from
NMR, XAS, and structural modeling that sheds light on the identity
of the CuĀ(I) binding site of a Ctr1 model peptide. The CuĀ(I) site
includes the same <i>bis</i>-His site identified in previous
work to facilitate ascorbate-dependent CuĀ(II) reduction. The data
presented here are consistent with a rational mechanism by which Ctr1
provides coordination environments that facilitate CuĀ(II) reduction
prior to CuĀ(I) transport
Model Peptide Studies Reveal a Mixed Histidine-Methionine Cu(I) Binding Site at the NāTerminus of Human Copper Transporter 1
Copper
is a vital metal cofactor in enzymes that are essential to myriad
biological processes. Cellular acquisition of copper is primarily
accomplished through the Ctr family of plasma membrane copper transport
proteins. Model peptide studies indicate that the human Ctr1 N-terminus
binds to CuĀ(II) with high affinity through an amino terminal CuĀ(II),
NiĀ(II) (ATCUN) binding site. Unlike typical ATCUN-type peptides, the
Ctr1 peptide facilitates the ascorbate-dependent reduction of CuĀ(II)
bound in its ATCUN site by virtue of an adjacent HH (<i>bis</i>-His) sequence in the peptide. It is likely that the CuĀ(I) coordination
environment influences the redox behavior of Cu bound to this peptide;
however, the identity and coordination geometry of the CuĀ(I) site
has not been elucidated from previous work. Here, we show data from
NMR, XAS, and structural modeling that sheds light on the identity
of the CuĀ(I) binding site of a Ctr1 model peptide. The CuĀ(I) site
includes the same <i>bis</i>-His site identified in previous
work to facilitate ascorbate-dependent CuĀ(II) reduction. The data
presented here are consistent with a rational mechanism by which Ctr1
provides coordination environments that facilitate CuĀ(II) reduction
prior to CuĀ(I) transport