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Research Interests of the Elliott Group
elliott@bu.edu
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| Bioinorganic
Chemistry - Bioelectrochemistry - Biophysical Chemistry
The Elliott Group,
investigates the interplay between biological systems
and redox-active species (e.g., metal ions, organic radicals, disulfide
bonds, reactive oxygen species), with an emphasis on investigating the kinetic
and thermodynamic basis for catalytic redox chemistry as well as the molecular
impact of metal ions and reactive oxygen species upon cells. The work in
the Elliott Group is always growing and evolving -- the descriptions below are
brief "snapshots" of our efforts. Please come back again to see what we're up to!
The direct electrochemical method of protein film voltammetry (PFV) is
currently employed in the lab for (1) the study of catalytic systems involved
in multiple electron-transfer steps; (2) the determination of redox behavior in
otherwise intractable systems; (3) the development novel electrodes for
use in either high-resolution chemical biology, or the energy sciences.
Our lab is also interested in the development of
a family of proteomic techniques for the assessment of the impact of
redox-active species (such as transition metals and reactive oxygen species)
within living systems in order to address questions of metal-ion import,
packaging, and co-factor synthesis. A few of these topics are described below
in further detail. |
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Bioelectrochemistry of Complex Metalloenzymes.
The Elliott Group uses electrochemical
tools, amongst others, to characterize the catalytic chemistry of redox active
enzymes that are involved in multiple electron transfer steps.
In particular, we use the technique of protein film voltammetry [PFV] to
observe the reduction potentials of redox-cofactors that are a part of the
essential machinery of an enzyme. Our laboratory interrogates a wide range of
proteins and enzymes using this technique, and questions we are interested in
vary from project to project. |
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Mechanisms of peroxidase catalysis have been investigated recently by our
group using PFV. The bacterial cytochrome c peroxidases contain two
heme groups (shown at left), one of which is a five-coordinate active site of
low reduction potential, and the other is a six-coordinate heme that is of
higher potential, which serves a role in intermolecular electron transfer. We
have certainly interrogated the enzyme from Nitrosomonas europaea, and
determined that electroactive films of "NeCcP" give an electrochemical
response indicating catalysis mediated by a n=1 ET step that is a part
of the catalytic cycle.
This work is supported by the National Institutes of Health.
Recent publications.
1. Bradley, A.L; Arciero, D.M.; Hooper, A.B.; Elliott, S.J.
"Protonation and inhibition of Cytochrome c Peroxidase from
Nitrosomonas europaea".
J. Inorg. Biochem. 2007, 101(1), 1733-1739. Which can be found
here.
2. Bradley, A.L.; Chobot, S.E.; Arciero, D.M.; Hooper, A.B.; Elliott,
S.J..
"A Distinctive Electrocatalytic Response from the Cytochrome c
Peroxidase of Nitrosomonas europaea".
J. Biol. Chem. 2004, 279(14): 13297-13300.Which can be found
here.
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Bacterial (multiheme) cytochromes are investigated in the Elliott
Group using PFV. These include complex enzymes, such as the siroheme-
dependent sulfite reductase, as well as simple cyt c-551 analogs and
the less-simple cyt c-554, a tetraheme cytochrome. The hemes of cyt
c-554 are shown at right.
This work is supported by the National Science Foundation.
Recent publications.
1.
Pulcu, G.S.; Elmore, B.L.; Arciero, D.M.; Hooper, A.B.;
"Direct electrochemistry of tetraheme cytochrome c-554 from
Nitrosomonas europaea: Redox cooperativity and conformational gating"
J. Am. Chem. Soc. 2007, 129(7),1838-1839. Which can be found
here.
2. Ye, T.; Kaur, R.; Wen, X.; Bren, K.L. Elliott,
S.J..
"Redox properties of wild-type and heme-binding loop mutants of bacterial
cytochromes c measured by direct electrochemistry".
Inorg. Chem. 2005, 44(24): 8999-9006. Which can be found
here.
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| The Redox
Chemistry of Flavo- and Disulfide-enzymes. Other projects in the lab
use electrochemistry as a way to probe the redox chemistry of enzymes involved
in oxidative stress response, such as thioredoxin, glutaredoxin and
thioredoxin reductases. This proven challenging due to the latent poor
electrochemistry of disulfides, and the potential instability of flavo-proteins.
However, we have been able to
investigate a wide range of proteins such as thioredoxins and thioredoxin
reductases. Thioredoxins are ubiquitous proteins that are small (~12 kDa),
utilizing a surface-exposed disulfide bond as their means of storing and
transferring electrons. Reduced thioredoxin is generated by a Trx reductase;
a structure of the E. coli is shown at right.
This work is supported by the Richard Allan Barry Fund of the Boston Foundation.
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