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PDBsum entry 1odn
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Oxidoreductase
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PDB id
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1odn
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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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Crystallographic studies on the reaction of isopenicillin n synthase with an unsaturated substrate analogue.
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Authors
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J.M.Elkins,
P.J.Rutledge,
N.I.Burzlaff,
I.J.Clifton,
R.M.Adlington,
P.L.Roach,
J.E.Baldwin.
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Ref.
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Org Biomol Chem, 2003,
1,
1455-1460.
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PubMed id
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Abstract
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Isopenicillin N synthase (IPNS) catalyses conversion of the linear tripeptide
delta-(L-alpha-aminoadipoyl)-L-cysteinyl-D-valine (ACV) to isopenicillin N
(IPN), the central step in biosynthesis of the beta-lactam antibiotics. The
unsaturated substrate analogue
delta-(L-alpha-aminoadipoyl)-L-cysteinyl-D-vinylglycine (ACvG) has previously
been incubated with IPNS and single product was isolated, a
2-alpha-hydroxymethyl isopenicillin N (HMPen), formed via a monooxygenase mode
of reactivity. ACvG has now been crystallised with IPNS and the structure of the
anaerobic IPNS:Fe(II):ACvG complex determined to 1.15 A resolution. Furthermore,
by exposing the anaerobically grown crystals to high-pressure oxygen gas, a
structure corresponding to the bicyclic product HMPen has been obtained at 1.60
A resolution. In light of these and other IPNS structures, and recent
developments with related dioxygenases, the [2 + 2] cycloaddition mechanism for
HMPen formation from ACvG has been revised, and a stepwise radical mechanism is
proposed. This revised mechanism remains consistent with the observed
stereospecificity of the transformation, but fits better with apparent
constraints on the coordination geometry around the active site iron atom.
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Secondary reference #1
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Title
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The reaction cycle of isopenicillin n synthase observed by X-Ray diffraction.
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Authors
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N.I.Burzlaff,
P.J.Rutledge,
I.J.Clifton,
C.M.Hensgens,
M.Pickford,
R.M.Adlington,
P.L.Roach,
J.E.Baldwin.
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Ref.
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Nature, 1999,
401,
721-724.
[DOI no: ]
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PubMed id
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Figure 2.
Figure 2 Proposed mechanisms for the oxidation of ACV and
ACmC to bicyclic and monocyclic products, respectively. See text
for details of compounds 1-6. AA, L-  -(
 -aminoadipoyl).
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Figure 3.
Figure 3 Stereo views of the two substrates and two products
overlaid. The key regions that participate in the reaction and
the iron atom (orange) are shown; the aminoadipoyl side chain,
which does not move significantly, is omitted for clarity. Shown
are ACV (white), IPN (yellow), ACmC (blue) and its monocyclic
sulphoxide product (pink). Figures were prepared using the
programs MOLSCRIPT20 and Raster3D (ref. 21).
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The above figures are
reproduced from the cited reference
with permission from Macmillan Publishers Ltd
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Secondary reference #2
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Title
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Structure of isopenicillin n synthase complexed with substrate and the mechanism of penicillin formation.
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Authors
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P.L.Roach,
I.J.Clifton,
C.M.Hensgens,
N.Shibata,
C.J.Schofield,
J.Hajdu,
J.E.Baldwin.
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Ref.
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Nature, 1997,
387,
827-830.
[DOI no: ]
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PubMed id
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Figure 2.
Figure 2 Mechanism for isopenicillin N formation and the
formation of the Fe: ACV: NO:. sp;IPNS complex.
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Figure 3.
Figure 3 Comparison of the structures of Mn: IPNS (a) and
Fe(II): ACV: IPNS (. b) from the same orientation. The
jelly-roll motif is in green, the C-terminal region (residues
313-331) cyan, the active-site metal ion (manganese in a, iron
in b) orange, the key substrate-binding residues (His 214, His
270, Asp 216, Arg 87, Arg 279, Tyr 189 and Ser 281) magenta, and
the ACV yellow.
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The above figures are
reproduced from the cited reference
with permission from Macmillan Publishers Ltd
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Secondary reference #3
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Title
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Crystal structure of isopenicillin n synthase is the first from a new structural family of enzymes.
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Authors
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P.L.Roach,
I.J.Clifton,
V.Fülöp,
K.Harlos,
G.J.Barton,
J.Hajdu,
I.Andersson,
C.J.Schofield,
J.E.Baldwin.
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Ref.
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Nature, 1995,
375,
700-704.
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PubMed id
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