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PDBsum entry 1kf6
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Oxidoreductase
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PDB id
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1kf6
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Contents |
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577 a.a.
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243 a.a.
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130 a.a.
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119 a.a.
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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Crystallographic studies of the escherichia coli quinol-Fumarate reductase with inhibitors bound to the quinol-Binding site.
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Authors
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T.M.Iverson,
C.Luna-Chavez,
L.R.Croal,
G.Cecchini,
D.C.Rees.
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Ref.
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J Biol Chem, 2002,
277,
16124-16130.
[DOI no: ]
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PubMed id
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Abstract
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The quinol-fumarate reductase (QFR) respiratory complex of Escherichia coli is a
four-subunit integral-membrane complex that catalyzes the final step of
anaerobic respiration when fumarate is the terminal electron acceptor. The
membrane-soluble redox-active molecule menaquinol (MQH(2)) transfers electrons
to QFR by binding directly to the membrane-spanning region. The crystal
structure of QFR contains two quinone species, presumably MQH(2), bound to the
transmembrane-spanning region. The binding sites for the two quinone molecules
are termed Q(P) and Q(D), indicating their positions proximal (Q(P)) or distal
(Q(D)) to the site of fumarate reduction in the hydrophilic flavoprotein and
iron-sulfur protein subunits. It has not been established whether both of these
sites are mechanistically significant. Co-crystallization studies of the E. coli
QFR with the known quinol-binding site inhibitors
4,6-dinitrophenol establish that both inhibitors block the binding of MQH(2) at
the Q(P) site. In the structures with the inhibitor bound at Q(P), no density is
observed at Q(D), which suggests that the occupancy of this site can vary and
argues against a structurally obligatory role for quinol binding to Q(D). A
comparison of the Q(P) site of the E. coli enzyme with quinone-binding sites in
other respiratory enzymes shows that an acidic residue is structurally
conserved. This acidic residue, Glu-C29, in the E. coli enzyme may act as a
proton shuttle from the quinol during enzyme turnover.
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Figure 1.
Fig. 1. Polypeptide -fold and electron transfer distances
in QFR. A, ribbon diagram views of the E. coli QFR separated by
a 90° rotation about a vertical axis. The flavoprotein is
shown in blue, the iron protein is in red, and the transmembrane
anchors are in dark green (FrdC) and purple (FrdD). The
approximate boundary of the membrane is indicated with a black
line. B, inter-cofactor distances of the E. coli enzyme. The
known cofactors are superimposed onto an outline of the enzyme.
C, inter-cofactor distances in the W. succinogenes enzyme. The
b-type hemes associated with the membrane anchor reduce the
electron transfer distance between a predicted distal
quinol-binding site (data not shown). Figs. 1, 3, and 4 were
made using Molscript (56), Bobscript (57), and Raster3D (58).
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Figure 2.
Fig. 2. Chemical structures for oxidized menaquinone-8
(MQ-8) (A), reduced menaquinol-8 (B), HQNO (C), and DNP-19 (D).
MQ-8 is the primary menaquinone found in E. coli membranes, but
smaller proportions of MQ-6, MQ-7, and MQ-9 are additionally
present in the organism (59).
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The above figures are
reprinted
by permission from the ASBMB:
J Biol Chem
(2002,
277,
16124-16130)
copyright 2002.
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Secondary reference #1
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Title
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Structure of the escherichia coli fumarate reductase respiratory complex.
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Authors
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T.M.Iverson,
C.Luna-Chavez,
G.Cecchini,
D.C.Rees.
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Ref.
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Science, 1999,
284,
1961-1966.
[DOI no: ]
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PubMed id
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Figure 4.
Fig. 4. Quinone binding pockets and active site residues. (A)
Stereoview of the Q[P] binding site shows Q[P] is bound in a
polar pocket likely positioned just above the membrane bilayer.
(B) Stereoview of the Q[D] site shows Q[D] is in a relatively
apolar pocket within the membrane bilayer. (C) Binding site for
the physiological inhibitor oxaloacetate adjacent to the FAD.
Oxaloacetate lies beneath the isoalloxazine ring of the flavin.
The flavin ring and inhibitor are shown superimposed onto a
2|F[o]|  |F[c]|
map contoured at 1  . The
adenine has been omitted for clarity. Side chains that appear to
interact directly with the inhibitor are labeled.
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The above figure is
reproduced from the cited reference
with permission from the AAAs
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