Isopenicillin N synthase (IPNS) is a non-haem iron(II) oxidase which catalyses the biosynthesis of isopenicillin N from the tripeptide δ-(l-α-aminoadipoyl)-l-cysteinyl-d-valine (ACV). Herein we report crystallographic studies to investigate the reaction of IPNS with the truncated substrate analogue δ-(l-α-aminoadipoyl)-l-cysteinyl-d-α-aminobutyrate (ACAb). It has been reported previously that this analogue gives rise to three β-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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June 2003
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Research Article|
June 15 2003
Structural studies on the reaction of isopenicillin N synthase with the substrate analogue delta-(l-alpha-aminoadipoyl)-l-cysteinyl-d-alpha-aminobutyrate
Alexandra J. LONG;
Alexandra J. LONG
The Dyson Perrins Laboratory and the Oxford Centre for Molecular Sciences, University of Oxford, South Parks Road, Oxford OX1 3QY, U.K.
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Ian J. CLIFTON;
Ian J. CLIFTON
The Dyson Perrins Laboratory and the Oxford Centre for Molecular Sciences, University of Oxford, South Parks Road, Oxford OX1 3QY, U.K.
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Peter L. ROACH;
Peter L. ROACH
1
The Dyson Perrins Laboratory and the Oxford Centre for Molecular Sciences, University of Oxford, South Parks Road, Oxford OX1 3QY, U.K.
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Jack E. BALDWIN;
Jack E. BALDWIN
The Dyson Perrins Laboratory and the Oxford Centre for Molecular Sciences, University of Oxford, South Parks Road, Oxford OX1 3QY, U.K.
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Christopher J. SCHOFIELD;
Christopher J. SCHOFIELD
2
The Dyson Perrins Laboratory and the Oxford Centre for Molecular Sciences, University of Oxford, South Parks Road, Oxford OX1 3QY, U.K.
2To whom correspondence should be addressed (e-mail christopher.schofield@chem.ox.ac.uk or peter.rutledge@ucd.ie).
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Peter J. RUTLEDGE
The Dyson Perrins Laboratory and the Oxford Centre for Molecular Sciences, University of Oxford, South Parks Road, Oxford OX1 3QY, U.K.
2To whom correspondence should be addressed (e-mail christopher.schofield@chem.ox.ac.uk or peter.rutledge@ucd.ie).
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Publisher: Portland Press Ltd
Received:
October 18 2002
Revision Received:
March 04 2003
Accepted:
March 06 2003
Accepted Manuscript online:
March 06 2003
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London ©2003
2003
Biochem J (2003) 372 (3): 687–693.
Article history
Received:
October 18 2002
Revision Received:
March 04 2003
Accepted:
March 06 2003
Accepted Manuscript online:
March 06 2003
Citation
Alexandra J. LONG, Ian J. CLIFTON, Peter L. ROACH, Jack E. BALDWIN, Christopher J. SCHOFIELD, Peter J. RUTLEDGE; Structural studies on the reaction of isopenicillin N synthase with the substrate analogue delta-(l-alpha-aminoadipoyl)-l-cysteinyl-d-alpha-aminobutyrate. Biochem J 15 June 2003; 372 (3): 687–693. doi: https://doi.org/10.1042/bj20021627
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