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PDBsum entry 1oc1
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Oxidoreductase
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PDB id
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1oc1
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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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Structural studies on the reaction of isopenicillin n synthase with the substrate analogue delta-(L-Alpha-Aminoadipoyl)-L-Cysteinyl-D-Alpha-Aminobutyrate.
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Authors
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A.J.Long,
I.J.Clifton,
P.L.Roach,
J.E.Baldwin,
C.J.Schofield,
P.J.Rutledge.
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Ref.
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Biochem J, 2003,
372,
687-693.
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PubMed id
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Abstract
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Isopenicillin N synthase (IPNS) is a non-haem iron(II) oxidase which catalyses
the biosynthesis of isopenicillin N from the tripeptide
delta-(L-alpha-aminoadipoyl)-L-cysteinyl-D-valine (ACV). Herein we report
crystallographic studies to investigate the reaction of IPNS with the truncated
substrate analogue
delta-(L-alpha-aminoadipoyl)-L-cysteinyl-D-alpha-aminobutyrate (ACAb). It has
been reported previously that this analogue gives rise to three beta-lactam
products when incubated with IPNS: two methyl penams and a cepham. Crystal
structures of the IPNS-Fe(II)-ACAb and IPNS-Fe(II)-ACAb-NO complexes have now
been solved and are reported herein. These structures and modelling studies
based on them shed light on the diminished product selectivity shown by IPNS in
its reaction with ACAb and further rationalize the presence of certain key
residues at the IPNS active site.
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Secondary reference #1
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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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