1hb4
From Proteopedia
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|PDB= 1hb4 |SIZE=350|CAPTION= <scene name='initialview01'>1hb4</scene>, resolution 1.50Å | |PDB= 1hb4 |SIZE=350|CAPTION= <scene name='initialview01'>1hb4</scene>, resolution 1.50Å | ||
|SITE= <scene name='pdbsite=SCV:Active+Site+(Fe+Binding)'>SCV</scene> | |SITE= <scene name='pdbsite=SCV:Active+Site+(Fe+Binding)'>SCV</scene> | ||
| - | |LIGAND= | + | |LIGAND= <scene name='pdbligand=FE2:FE+(II)+ION'>FE2</scene>, <scene name='pdbligand=SCV:N6-[(1S)-2-{[(1R)-1-CARBOXY-2-METHYLPROPYL]OXY}-1-(MERCAPTOCARBONYL)-2-OXOETHYL]-6-OXO-L-LYSINE'>SCV</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene> |
|ACTIVITY= | |ACTIVITY= | ||
|GENE= PCB C ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=162425 Emericella nidulans]) | |GENE= PCB C ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=162425 Emericella nidulans]) | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY= | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1hb4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1hb4 OCA], [http://www.ebi.ac.uk/pdbsum/1hb4 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1hb4 RCSB]</span> | ||
}} | }} | ||
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[[Category: Roach, P L.]] | [[Category: Roach, P L.]] | ||
[[Category: Rutledge, P J.]] | [[Category: Rutledge, P J.]] | ||
| - | [[Category: FE2]] | ||
| - | [[Category: SCV]] | ||
| - | [[Category: SO4]] | ||
[[Category: antibiotic biosynthesis]] | [[Category: antibiotic biosynthesis]] | ||
[[Category: b-lactam antibiotic]] | [[Category: b-lactam antibiotic]] | ||
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[[Category: penicillin biosynthesis]] | [[Category: penicillin biosynthesis]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 21:01:29 2008'' |
Revision as of 18:01, 30 March 2008
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| , resolution 1.50Å | |||||||
|---|---|---|---|---|---|---|---|
| Sites: | |||||||
| Ligands: | , , | ||||||
| Gene: | PCB C (Emericella nidulans) | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
ISOPENICILLIN N SYNTHASE FROM ASPERGILLUS NIDULANS (OXYGEN EXPOSED PRODUCT FROM ANAEROBIC ACOV FE COMPLEX)
Overview
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.
About this Structure
1HB4 is a Single protein structure of sequence from Emericella nidulans. Full crystallographic information is available from OCA.
Reference
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
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