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| [[Image:1hb4.gif|left|200px]] | | {{Seed}} |
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| {{STRUCTURE_1hb4| PDB=1hb4 | SCENE= }} | | {{STRUCTURE_1hb4| PDB=1hb4 | SCENE= }} |
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| '''ISOPENICILLIN N SYNTHASE FROM ASPERGILLUS NIDULANS (OXYGEN EXPOSED PRODUCT FROM ANAEROBIC ACOV FE COMPLEX)'''
| | ===ISOPENICILLIN N SYNTHASE FROM ASPERGILLUS NIDULANS (OXYGEN EXPOSED PRODUCT FROM ANAEROBIC ACOV FE COMPLEX)=== |
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| ==Overview==
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| BACKGROUND: Isopenicillin N synthase (IPNS) catalyses formation of bicyclic isopenicillin N, precursor to all penicillin and cephalosporin antibiotics, from the linear tripeptide delta-(L-alpha-aminoadipoyl)-L-cysteinyl-D-valine. IPNS is a non-haem iron(II)-dependent enzyme which utilises the full oxidising potential of molecular oxygen in catalysing the bicyclisation reaction. The reaction mechanism is believed to involve initial formation of the beta-lactam ring (via a thioaldehyde intermediate) to give an iron(IV)-oxo species, which then mediates closure of the 5-membered thiazolidine ring. RESULTS: Here we report experiments employing time-resolved crystallography to observe turnover of an isosteric substrate analogue designed to intercept the catalytic pathway at an early stage. Reaction in the crystalline enzyme-substrate complex was initiated by the application of high-pressure oxygen, and subsequent flash freezing allowed an oxygenated product to be trapped, bound at the iron centre. A mechanism for formation of the observed thiocarboxylate product is proposed. CONCLUSIONS: In the absence of its natural reaction partner (the N-H proton of the L-cysteinyl-D-valine amide bond), the proposed hydroperoxide intermediate appears to attack the putative thioaldehyde species directly. These results shed light on the events preceding beta-lactam closure in the IPNS reaction cycle, and enhance our understanding of the mechanism for reaction of the enzyme with its natural substrate.
| | The line below this paragraph, {{ABSTRACT_PUBMED_11755401}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 11755401 is the PubMed ID number. |
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| | {{ABSTRACT_PUBMED_11755401}} |
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| ==About this Structure== | | ==About this Structure== |
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| [[Category: Oxygenase]] | | [[Category: Oxygenase]] |
| [[Category: Penicillin biosynthesis]] | | [[Category: Penicillin biosynthesis]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 18:39:33 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 1 07:55:41 2008'' |
