1hb4 | pdb_00001hb4

ISOPENICILLIN N SYNTHASE FROM ASPERGILLUS NIDULANS (OXYGEN EXPOSED PRODUCT FROM ANAEROBIC ACOV FE COMPLEX)

spinqualitylabelsall models 1hb4, resolution 1.50Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 1hb4 is a 1 chain structure with sequence from A. nidulans. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: FE2, SCV, SO4 Related: 1bk0, 1blz, 1hb1, 1hb2, 1hb3, 1ips, 1qiq, 1qje, 1qjf Gene: PCB C (A. nidulans) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [IPNS_EMENI] Removes, in the presence of oxygen, 4 hydrogen atoms from delta-L-(alpha-aminoadipyl)-L-cysteinyl-D-valine (ACV) to form the azetidinone and thiazolidine rings of isopenicillin. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed 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. Alternative oxidation by isopenicillin N synthase observed by X-ray diffraction.,Ogle JM, Clifton IJ, Rutledge PJ, Elkins JM, Burzlaff NI, Adlington RM, Roach PL, Baldwin JE Chem Biol. 2001 Dec;8(12):1231-7. PMID:11755401 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Isopenicillin N synthase

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