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PDBsum entry 2vpa
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Oxidoreductase
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PDB id
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2vpa
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References listed in PDB file
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Key reference
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Title
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High-Resolution structure of the antibiotic resistance protein nima from deinococcus radiodurans.
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Authors
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H.K.Leiros,
C.Tedesco,
S.M.Mcsweeney.
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Ref.
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Acta Crystallogr Sect F Struct Biol Cryst Commun, 2008,
64,
442-447.
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PubMed id
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Abstract
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Many anaerobic human pathogenic bacteria are treated using
5-nitroimidazole-based (5-Ni) antibiotics, a class of inactive prodrugs that
contain a nitro group. The nitro group must be activated in an anaerobic
one-electron reduction and is therefore dependent on the redox system in the
target cells. Antibiotic resistance towards 5-Ni drugs is found to be related to
the nim genes (nimA, nimB, nimC, nimD, nimE and nimF), which are proposed to
encode a reductase that is responsible for converting the nitro group of the
antibiotic into a nonbactericidal amine. A mechanism for the Nim enzyme has been
proposed in which two-electron reduction of the nitro group leads to the
generation of nontoxic derivatives and confers resistance against these
antibiotics. The cofactor was found to be important in the mechanism and was
found to be covalently linked to the reactive His71. In this paper, the 1.2 A
atomic resolution crystal structure of the 5-nitroimidazole antibiotic
resistance protein NimA from Deinococcus radiodurans (DrNimA) is presented. A
planar cofactor is clearly visible and well defined in the electron-density map
adjacent to His71, the identification of the cofactor and its properties are
discussed.
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Secondary reference #1
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Title
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Structural basis of 5-Nitroimidazole antibiotic resistance: the crystal structure of nima from deinococcus radiodurans.
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Authors
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H.K.Leiros,
S.Kozielski-Stuhrmann,
U.Kapp,
L.Terradot,
G.A.Leonard,
S.M.Mcsweeney.
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Ref.
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J Biol Chem, 2004,
279,
55840-55849.
[DOI no: ]
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PubMed id
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Figure 5.
FIG. 5. a, Fourier difference map (F[o] - F[c]) at 3  with the
pyruvate residue omitted from the refinement of the native
drNimA structure. The finally refined pyruvate is given along
with some surrounding residues. b, a LIGPLOT (41) presentation
of the chemical environments of the pyruvate in the final drNimA
structure, with inter-atomic distances for polar interactions.
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Figure 7.
FIG. 7. Proposed antibiotic resistance mechanism. Step  ,
this is from the native drNimA structure to the covalently bound
pyruvate structure (drNimA-Pyr), an oxidation of His-71 and
pyruvate into a His-71-Pyr residue, a reaction that releases
2e^- and H+. Step  ,
the released electrons can further be used to reduce the
antibiotic. Because the antibiotic gets 2e^-, it prevents
formation of the toxic bactericidal radical  as
given in Fig. 1. Our drNimA-MTR structure seems to be an
intermediate, which is located somewhere along Step in
between the native drNimA and the drNimA-Pyr complex.
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The above figures are
reproduced from the cited reference
with permission from the ASBMB
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