This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.
Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.
1qjf
From Proteopedia
| Line 29: | Line 29: | ||
[[Category: sulfoxide]] | [[Category: sulfoxide]] | ||
| - | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 5 | + | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 5 17:00:44 2007'' |
Revision as of 14:55, 5 November 2007
|
ISOPENICILLIN N SYNTHASE FROM ASPERGILLUS NIDULANS (MONOCYCLIC SULFOXIDE-FE COMPLEX)
Overview
Isopenicillin N synthase (IPNS), a non-haem iron-dependent oxidase, catalyses the biosynthesis of isopenicillin N (IPN), the precursor of all, penicillins and cephalosporins. The key steps in this reaction are the two, iron-dioxygen-mediated ring closures of the tripeptide, delta-(L-alpha-aminoadipoyl)-L-cysteinyl-D-valine (ACV). It has been, proposed that the four-membered beta-lactam ring forms initially, associated with a highly oxidized iron(iv)-oxo (ferryl) moiety, which, subsequently mediates closure of the five-membered thiazolidine ring. Here, we describe observation of the IPNS reaction in crystals by X-ray, crystallography. IPNS Fe2+ substrate crystals were grown anaerobically, exposed to high pressures of oxygen to promote reaction and frozen, and, their structures were elucidated by X-ray diffraction. Using the natural, substrate ACV, this resulted in the IPNS x Fe2+ x IPN product complex., With the substrate analogue, delta-(L-alpha-aminoadipoyl)-L-cysteinyl-L-S-methylcysteine (ACmC) in the, crystal, the reaction cycle was interrupted at the monocyclic stage. These, mono- and bicyclic structures support our hypothesis of a two-stage, reaction sequence leading to penicillin. Furthermore, the formation of a, monocyclic sulphoxide product from ACmC is most simply explained by the, interception of a high-valency iron-oxo species.
About this Structure
1QJF is a Single protein structure of sequence from Emericella nidulans with SO4, FE2 and ACS as ligands. Structure known Active Site: SA. Full crystallographic information is available from OCA.
Reference
The reaction cycle of isopenicillin N synthase observed by X-ray diffraction., Burzlaff NI, Rutledge PJ, Clifton IJ, Hensgens CM, Pickford M, Adlington RM, Roach PL, Baldwin JE, Nature. 1999 Oct 14;401(6754):721-4. PMID:10537113
Page seeded by OCA on Mon Nov 5 17:00:44 2007
