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PDBsum entry 1kqb
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Oxidoreductase
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PDB id
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1kqb
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Contents |
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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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Structures of nitroreductase in three states: effects of inhibitor binding and reduction.
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Authors
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C.A.Haynes,
R.L.Koder,
A.F.Miller,
D.W.Rodgers.
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Ref.
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J Biol Chem, 2002,
277,
11513-11520.
[DOI no: ]
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PubMed id
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Abstract
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The crystal structure of the nitroreductase enzyme from Enterobacter cloacae has
been determined for the oxidized form in separate complexes with benzoate and
acetate inhibitors and for the two-electron reduced form. Nitroreductase is a
member of a group of enzymes that reduce a broad range of nitroaromatic
compounds and has potential uses in chemotherapy and bioremediation. The
monomers of the nitroreductase dimer adopt an alpha+beta fold and together bind
two flavin mononucleotide prosthetic groups at the dimer interface. In the
oxidized enzyme, the flavin ring system adopts a strongly bent (16 degrees )
conformation, and the bend increases (25 degrees ) in the reduced form of the
enzyme, roughly the conformation predicted for reduced flavin free in solution.
Because free oxidized flavin is planar, the induced bend in the oxidized enzyme
may favor reduction, and it may also account for the characteristic inability of
the enzyme to stabilize the one electron-reduced semiquinone flavin, which is
also planar. Both inhibitors bind over the pyrimidine and central rings of the
flavin in partially overlapping sites. Comparison of the two inhibitor complexes
shows that a portion of helix H6 can flex to accommodate the differently sized
inhibitors suggesting a mechanism for accommodating varied substrates.
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Figure 1.
Fig. 1. Overview of the nitroreductase fold. a, ribbons
diagram of the nitroreductase dimer showing the location of the
flavin mononucleotide prosthetic groups (yellow bonds) at the
dimer interface. The bound acetate molecule is shown with red
bonds. b, topology of nitroreductase. Panel a was prepared with
the program RIBBONS (78).
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Figure 4.
Fig. 4. Inhibitor binding to nitroreductase. a, binding
of acetate over the isoalloxazine ring system; b, binding of
benzoate over the isoalloxazine ring system. Averaged omit
density for both inhibitors is contoured at three times the
r.m.s. deviation of the map.
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The above figures are
reprinted
by permission from the ASBMB:
J Biol Chem
(2002,
277,
11513-11520)
copyright 2002.
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