1uzw
From Proteopedia
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[[Image:1uzw.gif|left|200px]] | [[Image:1uzw.gif|left|200px]] | ||
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'''ISOPENICILLIN N SYNTHASE WITH L-D-(A-AMINOADIPOYL)-L-CYSTEINYL-D-ISODEHYDROVALINE''' | '''ISOPENICILLIN N SYNTHASE WITH L-D-(A-AMINOADIPOYL)-L-CYSTEINYL-D-ISODEHYDROVALINE''' | ||
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[[Category: Grummitt, A R.]] | [[Category: Grummitt, A R.]] | ||
[[Category: Rutledge, P J.]] | [[Category: Rutledge, P J.]] | ||
| - | [[Category: | + | [[Category: Antibiotic biosynthesis]] |
| - | [[Category: | + | [[Category: B-lactam antibiotic]] |
| - | [[Category: | + | [[Category: Oxidoreductase]] |
| - | [[Category: | + | [[Category: Oxygenase]] |
| - | [[Category: | + | [[Category: Penicillin biosynthesis]] |
| - | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 11:55:03 2008'' | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | |
Revision as of 08:55, 3 May 2008
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. 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 Sat May 3 11:55:03 2008
