Type
one (T1) Cu sites deliver electrons to catalytic Cu active
sites: the mononuclear type two (T2) Cu site in nitrite reductases
(NiRs) and the trinuclear Cu cluster in the multicopper oxidases (MCOs).
The T1 Cu and the remote catalytic sites are connected via a Cys-His
intramolecular electron-transfer (ET) bridge, which contains two potential
ET pathways: P1 through the protein backbone and P2 through the H-bond
between the Cys and the His. The high covalency of the T1 Cu–S(Cys)
bond is shown here to activate the T1 Cu site for hole superexchange
via occupied valence orbitals of the bridge. This covalency-activated
electronic coupling (<i>H</i><sub>DA</sub>) facilitates
long-range ET through both pathways. These pathways can be selectively
activated depending on the geometric and electronic structure of the
T1 Cu site and thus the anisotropic covalency of the T1 Cu–S(Cys)
bond. In NiRs, blue (π-type) T1 sites utilize P1 and green (σ-type)
T1 sites utilize P2, with P2 being more efficient. Comparing the MCOs
to NiRs, the second-sphere environment changes the conformation of
the Cys-His pathway, which selectively activates <i>H</i><sub>DA</sub> for superexchange by blue π sites for efficient
turnover in catalysis. These studies show that a given protein bridge,
here Cys-His, provides different superexchange pathways and electronic
couplings depending on the anisotropic covalencies of the donor and
acceptor metal sites