1uzw
From Proteopedia
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==Overview== | ==Overview== | ||
| - | Isopenicillin N synthase (IPNS) is a non-haem iron oxidase that catalyses | + | Isopenicillin N synthase (IPNS) is a non-haem iron oxidase that catalyses the formation of bicyclic isopenicillin N from delta-(L-alpha-aminoadipoyl)-L-cysteinyl-D-valine (ACV). In this study we report a novel activity for the iron of the IPNS active site, which behaves as a Lewis acid to catalyse the elimination of HF from the fluorinated substrate analogue, delta-(L-alpha-aminoadipoyl)-L-cysteinyl-D-beta-fluorovaline (ACbetaFV). X-Ray crystallographic studies of IPNS crystals grown anaerobically with ACbetaFV reveal that the valinyl beta-fluorine is missing from the active site region, and suggest the presence of the unsaturated tripeptide delta-(L-alpha-aminoadipoyl)-L-cysteinyl-D-isodehydrovaline in place of substrate ACbetaFV. (19)F NMR studies confirm the release of fluoride from ACbetaFV in the presence of the active IPNS enzyme. These results suggest a new mode of reactivity for the IPNS iron centre, a mechanism of action that has not previously been reported for any of the iron oxidase enzymes. |
==About this Structure== | ==About this Structure== | ||
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[[Category: Isopenicillin-N synthase]] | [[Category: Isopenicillin-N synthase]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Baldwin, J | + | [[Category: Baldwin, J E.]] |
| - | [[Category: Clifton, I | + | [[Category: Clifton, I J.]] |
| - | [[Category: Grummitt, A | + | [[Category: Grummitt, A R.]] |
| - | [[Category: Rutledge, P | + | [[Category: Rutledge, P J.]] |
[[Category: CDH]] | [[Category: CDH]] | ||
[[Category: FE2]] | [[Category: FE2]] | ||
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[[Category: penicillin biosynthesis]] | [[Category: penicillin biosynthesis]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:30:10 2008'' |
Revision as of 13:30, 21 February 2008
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ISOPENICILLIN N SYNTHASE WITH L-D-(A-AMINOADIPOYL)-L-CYSTEINYL-D-ISODEHYDROVALINE
Overview
Isopenicillin N synthase (IPNS) is a non-haem iron oxidase that catalyses the formation of bicyclic isopenicillin N from delta-(L-alpha-aminoadipoyl)-L-cysteinyl-D-valine (ACV). In this study we report a novel activity for the iron of the IPNS active site, which behaves as a Lewis acid to catalyse the elimination of HF from the fluorinated substrate analogue, delta-(L-alpha-aminoadipoyl)-L-cysteinyl-D-beta-fluorovaline (ACbetaFV). X-Ray crystallographic studies of IPNS crystals grown anaerobically with ACbetaFV reveal that the valinyl beta-fluorine is missing from the active site region, and suggest the presence of the unsaturated tripeptide delta-(L-alpha-aminoadipoyl)-L-cysteinyl-D-isodehydrovaline in place of substrate ACbetaFV. (19)F NMR studies confirm the release of fluoride from ACbetaFV in the presence of the active IPNS enzyme. These results suggest a new mode of reactivity for the IPNS iron centre, a mechanism of action that has not previously been reported for any of the iron oxidase enzymes.
About this Structure
1UZW is a Single protein structure of sequence from Emericella nidulans with , and as ligands. Active as Isopenicillin-N synthase, with EC number 1.21.3.1 Known structural/functional Site: . Full crystallographic information is available from OCA.
Reference
Active-site-mediated elimination of hydrogen fluoride from a fluorinated substrate analogue by isopenicillin N synthase., Grummitt AR, Rutledge PJ, Clifton IJ, Baldwin JE, Biochem J. 2004 Sep 1;382(Pt 2):659-66. PMID:15175003
Page seeded by OCA on Thu Feb 21 15:30:10 2008
