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PDBsum entry 1zz8
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Oxidoreductase
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PDB id
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1zz8
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Contents |
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* Residue conservation analysis
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Enzyme class:
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E.C.1.11.1.23
- (S)-2-hydroxypropylphosphonic acid epoxidase.
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Reaction:
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(S)-2-hydroxypropylphosphonate + H2O2 = (1R,2S)-epoxypropylphosphonate + 2 H2O
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(S)-2-hydroxypropylphosphonate
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+
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H2O2
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=
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(1R,2S)-epoxypropylphosphonate
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+
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2
×
H2O
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Cofactor:
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Fe cation
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Molecule diagrams generated from .mol files obtained from the
KEGG ftp site
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DOI no:
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Nature
437:838-844
(2005)
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PubMed id:
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Structural insight into antibiotic fosfomycin biosynthesis by a mononuclear iron enzyme.
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L.J.Higgins,
F.Yan,
P.Liu,
H.W.Liu,
C.L.Drennan.
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ABSTRACT
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The biosynthetic pathway of the clinically important antibiotic fosfomycin uses
enzymes that catalyse reactions without precedent in biology. Among these is
hydroxypropylphosphonic acid epoxidase, which represents a new subfamily of
non-haem mononuclear iron enzymes. Here we present six X-ray structures of this
enzyme: the apoenzyme at 2.0 A resolution; a native Fe(II)-bound form at 2.4 A
resolution; a tris(hydroxymethyl)aminomethane-Co(II)-enzyme complex structure at
1.8 A resolution; a substrate-Co(II)-enzyme complex structure at 2.5 A
resolution; and two substrate-Fe(II)-enzyme complexes at 2.1 and 2.3 A
resolution. These structural data lead us to suggest how this enzyme is able to
recognize and respond to its substrate with a conformational change that
protects the radical-based intermediates formed during catalysis. Comparisons
with other family members suggest why substrate binding is able to prime iron
for dioxygen binding in the absence of alpha-ketoglutarate (a co-substrate
required by many mononuclear iron enzymes), and how the unique epoxidation
reaction of hydroxypropylphosphonic acid epoxidase may occur.
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Selected figure(s)
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Figure 1.
Figure 1: Fosfomycin biosynthesis. The fosfomycin
biosynthetic pathway requires phosphoenolpyruvate mutase (Fom1),
phosphonopyruvate decarboxylase (Fom2), phosphonoacetaldehyde
methyltransferase (Fom3) and HppE (Fom4). 1, phosphoenolpyruvate
(PEP); 2, phosphonopyruvate (PnPy); 3, phosphonoacetaldehyde
(PnAA); 4, (S)-2-hydroxypropylphosphonic acid (S-HPP); 5,
fosfomycin. C1 and C2 positions are shown in blue.
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Figure 2.
Figure 2: Overall structure of Fe(ii)-HppE. a, An HppE
monomer consists of an  -domain
(blue), an interdomain linker (green) to a single  -strand
1 (cyan) and a -domain
(blue). This stereoview highlights the cantilever hairpin ( -strands
2 and 3) in cyan, facial triad ligands (Glu 142, His 138 and His
180) in ball-and-stick, and iron as a brown sphere. Helices and
strands are numbered separately and sequentially with respect to
the primary structure. b, HppE tetramer, coloured by molecule,
is shown down one of the three two-fold axes of symmetry. The
cantilever hairpin is coloured cyan in the blue molecule,
magenta in the red molecule, dark yellow in the yellow molecule,
and dark green in the green molecule. c, HppE tetramer oriented
along a second two-fold axis of symmetry, orthogonal to that in
b. The cantilever hairpins are coloured as in b. Figs 2-4 were
made in PyMol31.
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The above figures are
reprinted
by permission from Macmillan Publishers Ltd:
Nature
(2005,
437,
838-844)
copyright 2005.
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Figures were
selected
by the author.
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See
for a structure of this enzyme containing Zn(2+) in the active site.
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Literature references that cite this PDB file's key reference
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PubMed id
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Reference
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E.R.Farquhar,
J.P.Emerson,
K.D.Koehntop,
M.F.Reynolds,
M.Trmčić,
and
L.Que
(2011).
In vivo self-hydroxylation of an iron-substituted manganese-dependent extradiol cleaving catechol dioxygenase.
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J Biol Inorg Chem,
16,
589-597.
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P.K.Sydor,
S.M.Barry,
O.M.Odulate,
F.Barona-Gomez,
S.W.Haynes,
C.Corre,
L.Song,
and
G.L.Challis
(2011).
Regio- and stereodivergent antibiotic oxidative carbocyclizations catalysed by Rieske oxygenase-like enzymes.
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Nat Chem,
3,
388-392.
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W.Lu,
N.Roongsawang,
and
T.Mahmud
(2011).
Biosynthetic studies and genetic engineering of pactamycin analogs with improved selectivity toward malarial parasites.
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Chem Biol,
18,
425-431.
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J.Dawlaty,
X.Zhang,
M.A.Fischbach,
and
J.Clardy
(2010).
Dapdiamides, tripeptide antibiotics formed by unconventional amide ligases.
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J Nat Prod,
73,
441-446.
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P.Domínguez de María,
R.W.van Gemert,
A.J.Straathof,
and
U.Hanefeld
(2010).
Biosynthesis of ethers: unusual or common natural events?
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Nat Prod Rep,
27,
370-392.
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S.A.Borisova,
B.T.Circello,
J.K.Zhang,
W.A.van der Donk,
and
W.W.Metcalf
(2010).
Biosynthesis of rhizocticins, antifungal phosphonate oligopeptides produced by Bacillus subtilis ATCC6633.
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Chem Biol,
17,
28-37.
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J.T.Whitteck,
R.M.Cicchillo,
and
W.A.van der Donk
(2009).
Hydroperoxylation by hydroxyethylphosphonate dioxygenase.
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J Am Chem Soc,
131,
16225-16232.
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R.Latifi,
M.Bagherzadeh,
and
S.P.de Visser
(2009).
Origin of the correlation of the rate constant of substrate hydroxylation by nonheme iron(IV)-oxo complexes with the bond-dissociation energy of the C-H bond of the substrate.
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Chemistry,
15,
6651-6662.
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R.M.Cicchillo,
H.Zhang,
J.A.Blodgett,
J.T.Whitteck,
G.Li,
S.K.Nair,
W.A.van der Donk,
and
W.W.Metcalf
(2009).
An unusual carbon-carbon bond cleavage reaction during phosphinothricin biosynthesis.
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Nature,
459,
871-874.
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PDB code:
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W.W.Metcalf,
and
W.A.van der Donk
(2009).
Biosynthesis of phosphonic and phosphinic acid natural products.
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Annu Rev Biochem,
78,
65-94.
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J.W.Munos,
S.J.Moon,
S.O.Mansoorabadi,
W.Chang,
L.Hong,
F.Yan,
A.Liu,
and
H.W.Liu
(2008).
Purification and characterization of the epoxidase catalyzing the formation of fosfomycin from Pseudomonas syringae.
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Biochemistry,
47,
8726-8735.
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P.C.Bruijnincx,
G.van Koten,
and
R.J.Klein Gebbink
(2008).
Mononuclear non-heme iron enzymes with the 2-His-1-carboxylate facial triad: recent developments in enzymology and modeling studies.
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Chem Soc Rev,
37,
2716-2744.
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F.Yan,
S.J.Moon,
P.Liu,
Z.Zhao,
J.D.Lipscomb,
A.Liu,
and
H.W.Liu
(2007).
Determination of the substrate binding mode to the active site iron of (S)-2-hydroxypropylphosphonic acid epoxidase using 17O-enriched substrates and substrate analogues.
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Biochemistry,
46,
12628-12638.
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R.D.Woodyer,
G.Li,
H.Zhao,
and
W.A.van der Donk
(2007).
New insight into the mechanism of methyl transfer during the biosynthesis of fosfomycin.
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Chem Commun (Camb),
(),
359-361.
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F.Yan,
J.W.Munos,
P.Liu,
and
H.W.Liu
(2006).
Biosynthesis of fosfomycin, re-examination and re-confirmation of a unique Fe(II)- and NAD(P)H-dependent epoxidation reaction.
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Biochemistry,
45,
11473-11481.
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The most recent references are shown first.
Citation data come partly from CiteXplore and partly
from an automated harvesting procedure. Note that this is likely to be
only a partial list as not all journals are covered by
either method. However, we are continually building up the citation data
so more and more references will be included with time.
Where a reference describes a PDB structure, the PDB
code is
shown on the right.
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Links
