1QJE
Isopenicillin N synthase from Aspergillus nidulans (IP1 - Fe complex)
Summary for 1QJE
| Entry DOI | 10.2210/pdb1qje/pdb |
| Related | 1BK0 1QJF |
| Descriptor | ISOPENICILLIN N SYNTHASE, SULFATE ION, ISOPENICILLIN N, ... (6 entities in total) |
| Functional Keywords | b-lactam antibiotic, oxygenase, penicillin biosynthesis, enzyme-product complex |
| Biological source | Emericella nidulans (strain FGSC A4 / ATCC 38163 / CBS 112.46 / NRRL 194 / M139) (Aspergillus nidulans) |
| Total number of polymer chains | 1 |
| Total formula weight | 38438.57 |
| Authors | Burzlaff, N.I.,Clifton, I.J.,Rutledge, P.J.,Roach, P.L.,Adlington, R.M.,Baldwin, J.E. (deposition date: 1999-06-23, release date: 2000-06-29, Last modification date: 2024-05-08) |
| Primary citation | Burzlaff, N.I.,Rutledge, P.J.,Clifton, I.J.,Hensgens, C.M.H.,Pickford, M.,Adlington, R.M.,Roach, P.L.,Baldwin, J.E. The Reaction Cycle of Isopenicillin N Synthase Observed by X-Ray Diffraction Nature, 401:721-, 1999 Cited by PubMed Abstract: 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. PubMed: 10537113DOI: 10.1038/44400 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.35 Å) |
Structure validation
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