1hb2

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)

Structural highlights 1hb2 is a 1 chain structure with sequence from Emericella nidulans. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: , , Related: 1bk0, 1blz, 1ips, 1qiq, 1qje, 1qjf, 1hb1, 1hb3, 1hb4 Gene: PCB C (Emericella nidulans) Resources: FirstGlance, OCA, RCSB, PDBsum 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

spinqualitylabelsall models 1hb2, resolution 1.30Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image