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PDBsum entry 2bnm
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Oxidoreductase
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PDB id
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2bnm
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References listed in PDB file
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Key reference
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Title
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Structure and reactivity of hydroxypropylphosphonic acid epoxidase in fosfomycin biosynthesis by a cation- And flavin-Dependent mechanism.
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Authors
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K.Mcluskey,
S.Cameron,
F.Hammerschmidt,
W.N.Hunter.
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Ref.
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Proc Natl Acad Sci U S A, 2005,
102,
14221-14226.
[DOI no: ]
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PubMed id
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Abstract
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The biosynthesis of fosfomycin, an oxirane antibiotic in clinical use, involves
a unique epoxidation catalyzed by (S)-2-hydroxypropylphosphonic acid epoxidase
(HPPE). The reaction is essentially dehydrogenation of a secondary alcohol. A
high-resolution crystallographic analysis reveals that the HPPE subunit displays
a two-domain combination. The C-terminal or catalytic domain has the cupin fold
that binds a divalent cation, whereas the N-terminal domain carries a
helix-turn-helix motif with putative DNA-binding helices positioned 34 A apart.
The structure of HPPE serves as a model for numerous proteins, of ill-defined
function, predicted to be transcription factors but carrying a cupin domain at
the C terminus. Structure-reactivity analyses reveal conformational changes near
the catalytic center driven by the presence or absence of ligand, that HPPE is a
Zn(2+)/Fe(2+)-dependent epoxidase, proof that flavin mononucleotide is required
for catalysis, and allow us to propose a simple mechanism that is compatible
with previous experimental data. The participation of the redox inert Zn(2+) in
the mechanism is surprising and indicates that Lewis acid properties of the
metal ions are sufficient to polarize the substrate and, aided by flavin
mononucleotide reduction, facilitate the epoxidation.
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Figure 2.
Fig. 2. Molecular structure. (a) Ribbon diagram of the HPPE
subunit with  helices colored red and
 strands, blue. Zn2+ is
depicted as a sphere (magenta). (b) The functional tetramer
viewed down a crystallographic twofold axis. Subunits are
coloured red (A), blue (B), gold (C), and cyan (D). PYMOL (28)
was used for molecular images.
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Figure 4.
Fig. 4. A postulated mechanism for HPPE. States A and C are
represented by the structures HPPE-Zn and HPPE-Fos, respectively.
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Secondary reference #1
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Title
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Initiating a crystallographic analysis of recombinant (s)-2-Hydroxypropylphosphonic acid epoxidase from streptomyces wedmorensis.
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Authors
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S.Cameron,
K.Mcluskey,
R.Chamberlayne,
I.Hallyburton,
W.N.Hunter.
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Ref.
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Acta Crystallogr Sect F Struct Biol Cryst Commun, 2005,
61,
534-536.
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PubMed id
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Note: In the PDB file this reference is
annotated as "TO BE PUBLISHED". The citation details given above have
been manually determined.
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