Solvent Tuning of Electrochemical Potentials in the Active Sites of HiPIP Versus Ferredoxin
Abhishek Dey,1
Francis E. Jenney, Jr.,2
Michael W. W. Adams,2
Elena Babini,3
Yasuhiro Takahashi,4
Keiichi Fukuyama,4
Keith O. Hodgson,1,5*
Britt Hedman,5*
Edward I. Solomon1,5*
A persistent puzzle in the field of biological electron transfer
is the conserved iron-sulfur cluster motif in both high potential
iron-sulfur protein (HiPIP) and ferredoxin (Fd) active sites.
Despite this structural similarity, HiPIPs react oxidatively
at physiological potentials, whereas Fds are reduced. Sulfur
K-edge x-ray absorption spectroscopy uncovers the substantial
influence of hydration on this variation in reactivity. Fe-S
covalency is much lower in natively hydrated Fd active sites
than in HiPIPs but increases upon water removal; similarly,
HiPIP covalency decreases when unfolding exposes an otherwise
hydrophobically shielded active site to water. Studies on model
compounds and accompanying density functional theory calculations
support a correlation of Fe-S covalency with ease of oxidation
and therefore suggest that hydration accounts for most of the
difference between Fd and HiPIP reduction potentials.
2 Department of Biochemistry and Molecular Biology, University of Georgia, Athens, GA 30602, USA.
3 University of Bologna, Campus Universitario di Scienze degli Alimenti Via Ravennate, 1020, 47023 Cesena, Italy.
4 Department of Biological Sciences, Graduate School of Science, Osaka University, Toyonaka, Osaka 560-0043, Japan.
5 Stanford Synchrotron Radiation Laboratory (SSRL), Stanford Linear Accelerator Center (SLAC), Stanford University, Menlo Park, CA 94025, USA.
* To whom correspondence should be addressed. E-mail: hodgson{at}ssrl.slac.stanford.edu (K.O.H.); hedman{at}ssrl.slac.stanford.edu (B.H.); edward.solomon{at}stanford.edu (E.I.S.)
