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1hb3

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[[Image:1hb3.jpg|left|200px]]<br /><applet load="1hb3" size="350" color="white" frame="true" align="right" spinBox="true"
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[[Image:1hb3.jpg|left|200px]]
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caption="1hb3, resolution 1.40&Aring;" />
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'''ISOPENICILLIN N SYNTHASE FROM ASPERGILLUS NIDULANS (OXYGEN EXPOSED PRODUCT FROM ANAEROBIC ACOV FE COMPLEX)'''<br />
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{{Structure
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|PDB= 1hb3 |SIZE=350|CAPTION= <scene name='initialview01'>1hb3</scene>, resolution 1.40&Aring;
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|SITE= <scene name='pdbsite=SCV:Active+Site+(Fe+Binding)'>SCV</scene>
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|LIGAND= <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=FE2:FE+(II)+ION'>FE2</scene> and <scene name='pdbligand=SCV:N6-[(1S)-2-{[(1R)-1-CARBOXY-2-METHYLPROPYL]OXY}-1-(MERCAPTOCARBONYL)-2-OXOETHYL]-6-OXO-L-LYSINE'>SCV</scene>
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|ACTIVITY=
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|GENE= PCB C ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=162425 Emericella nidulans])
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}}
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'''ISOPENICILLIN N SYNTHASE FROM ASPERGILLUS NIDULANS (OXYGEN EXPOSED PRODUCT FROM ANAEROBIC ACOV FE COMPLEX)'''
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==Overview==
==Overview==
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==About this Structure==
==About this Structure==
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1HB3 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 <scene name='pdbligand=SO4:'>SO4</scene>, <scene name='pdbligand=FE2:'>FE2</scene> and <scene name='pdbligand=SCV:'>SCV</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Known structural/functional Site: <scene name='pdbsite=SCV:Active+Site+(Fe+Binding)'>SCV</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1HB3 OCA].
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1HB3 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Emericella_nidulans Emericella nidulans]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1HB3 OCA].
==Reference==
==Reference==
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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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=11755401 11755401]
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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:[http://www.ncbi.nlm.nih.gov/pubmed/11755401 11755401]
[[Category: Emericella nidulans]]
[[Category: Emericella nidulans]]
[[Category: Single protein]]
[[Category: Single protein]]
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[[Category: penicillin biosynthesis]]
[[Category: penicillin biosynthesis]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:59:22 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 11:34:42 2008''

Revision as of 09:34, 20 March 2008


PDB ID 1hb3

Drag the structure with the mouse to rotate
, resolution 1.40Å
Sites:
Ligands: , and
Gene: PCB C (Emericella nidulans)
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

1HB3 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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