1hb1: Difference between revisions
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[[Image:1hb1. | [[Image:1hb1.jpg|left|200px]]<br /><applet load="1hb1" size="450" color="white" frame="true" align="right" spinBox="true" | ||
<applet load="1hb1" size="450" color="white" frame="true" align="right" spinBox="true" | |||
caption="1hb1, resolution 1.55Å" /> | caption="1hb1, resolution 1.55Å" /> | ||
'''ISOPENICILLIN N SYNTHASE FROM ASPERGILLUS NIDULANS (ANAEROBIC ACOV FE COMPLEX)'''<br /> | '''ISOPENICILLIN N SYNTHASE FROM ASPERGILLUS NIDULANS (ANAEROBIC ACOV FE COMPLEX)'''<br /> | ||
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==About this Structure== | ==About this Structure== | ||
1HB1 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Emericella_nidulans Emericella nidulans] with SO4, FE2 and OCV as [http://en.wikipedia.org/wiki/ligands ligands]. | 1HB1 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Emericella_nidulans Emericella nidulans] with SO4, FE2 and OCV as [http://en.wikipedia.org/wiki/ligands ligands]. Known structural/functional Site: <scene name='pdbsite=OCV:Active Site (Fe Binding)'>OCV</scene>. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1HB1 OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: penicillin biosynthesis]] | [[Category: penicillin biosynthesis]] | ||
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Dec 18 16:12:53 2007'' | ||
Revision as of 17:03, 18 December 2007
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ISOPENICILLIN N SYNTHASE FROM ASPERGILLUS NIDULANS (ANAEROBIC ACOV FE COMPLEX)
OverviewOverview
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 StructureAbout this Structure
1HB1 is a Single protein structure of sequence from Emericella nidulans with SO4, FE2 and OCV as ligands. Known structural/functional Site: . Full crystallographic information is available from OCA.
ReferenceReference
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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