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1qje

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[[Image:1qje.jpg|left|200px]]
 
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==Isopenicillin N synthase from Aspergillus nidulans (IP1 - Fe complex)==
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The line below this paragraph, containing "STRUCTURE_1qje", creates the "Structure Box" on the page.
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<StructureSection load='1qje' size='340' side='right'caption='[[1qje]], [[Resolution|resolution]] 1.35&Aring;' scene=''>
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[1qje]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Aspergillus_nidulans Aspergillus nidulans]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1QJE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1QJE FirstGlance]. <br>
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or leave the SCENE parameter empty for the default display.
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.35&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACV:L-D-(A-AMINOADIPOYL)-L-CYSTEINYL-D-VALINE'>ACV</scene>, <scene name='pdbligand=FE2:FE+(II)+ION'>FE2</scene>, <scene name='pdbligand=IP1:ISOPENICILLIN+N'>IP1</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
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{{STRUCTURE_1qje| PDB=1qje | SCENE= }}
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1qje FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1qje OCA], [https://pdbe.org/1qje PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1qje RCSB], [https://www.ebi.ac.uk/pdbsum/1qje PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1qje ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/IPNA_EMENI IPNA_EMENI] Isopenicillin N synthase; part of the gene cluster that mediates the biosynthesis of penicillin, the world's most important antibiotic (PubMed:3319778, PubMed:11755401). IpnA catalyzes the cyclization of the tripeptide N-[(5S)-5-amino-5-carboxypentanoyl]-L-cysteinyl-D-valine (LLD-ACV or ACV) to form isopenicillin N (IPN) that contains the beta-lactam nucleus (PubMed:3319778, PubMed:11755401, PubMed:28703303). The penicillin biosynthesis occurs via 3 enzymatic steps, the first corresponding to the production of the tripeptide N-[(5S)-5-amino-5-carboxypentanoyl]-L-cysteinyl-D-valine (LLD-ACV or ACV) by the NRPS acvA. The tripeptide ACV is then cyclized to isopenicillin N (IPN) by the isopenicillin N synthase ipnA that forms the beta-lactam nucleus. Finally, the alpha-aminoadipyl side chain is exchanged for phenylacetic acid by the isopenicillin N acyltransferase penDE to yield penicillin in the peroxisomal matrix (By similarity).[UniProtKB:P08703]<ref>PMID:11755401</ref> <ref>PMID:28703303</ref> <ref>PMID:3319778</ref>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/qj/1qje_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1qje ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Isopenicillin N synthase (IPNS), a non-haem iron-dependent oxidase, catalyses the biosynthesis of isopenicillin N (IPN), the precursor of all penicillins and cephalosporins. The key steps in this reaction are the two iron-dioxygen-mediated ring closures of the tripeptide delta-(L-alpha-aminoadipoyl)-L-cysteinyl-D-valine (ACV). It has been proposed that the four-membered beta-lactam ring forms initially, associated with a highly oxidized iron(iv)-oxo (ferryl) moiety, which subsequently mediates closure of the five-membered thiazolidine ring. Here we describe observation of the IPNS reaction in crystals by X-ray crystallography. IPNS Fe2+ substrate crystals were grown anaerobically, exposed to high pressures of oxygen to promote reaction and frozen, and their structures were elucidated by X-ray diffraction. Using the natural substrate ACV, this resulted in the IPNS x Fe2+ x IPN product complex. With the substrate analogue, delta-(L-alpha-aminoadipoyl)-L-cysteinyl-L-S-methylcysteine (ACmC) in the crystal, the reaction cycle was interrupted at the monocyclic stage. These mono- and bicyclic structures support our hypothesis of a two-stage reaction sequence leading to penicillin. Furthermore, the formation of a monocyclic sulphoxide product from ACmC is most simply explained by the interception of a high-valency iron-oxo species.
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'''ISOPENICILLIN N SYNTHASE FROM ASPERGILLUS NIDULANS (IP1-FE COMPLEX)'''
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The reaction cycle of isopenicillin N synthase observed by X-ray diffraction.,Burzlaff NI, Rutledge PJ, Clifton IJ, Hensgens CM, Pickford M, Adlington RM, Roach PL, Baldwin JE Nature. 1999 Oct 14;401(6754):721-4. PMID:10537113<ref>PMID:10537113</ref>
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==Overview==
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Isopenicillin N synthase (IPNS), a non-haem iron-dependent oxidase, catalyses the biosynthesis of isopenicillin N (IPN), the precursor of all penicillins and cephalosporins. The key steps in this reaction are the two iron-dioxygen-mediated ring closures of the tripeptide delta-(L-alpha-aminoadipoyl)-L-cysteinyl-D-valine (ACV). It has been proposed that the four-membered beta-lactam ring forms initially, associated with a highly oxidized iron(iv)-oxo (ferryl) moiety, which subsequently mediates closure of the five-membered thiazolidine ring. Here we describe observation of the IPNS reaction in crystals by X-ray crystallography. IPNS Fe2+ substrate crystals were grown anaerobically, exposed to high pressures of oxygen to promote reaction and frozen, and their structures were elucidated by X-ray diffraction. Using the natural substrate ACV, this resulted in the IPNS x Fe2+ x IPN product complex. With the substrate analogue, delta-(L-alpha-aminoadipoyl)-L-cysteinyl-L-S-methylcysteine (ACmC) in the crystal, the reaction cycle was interrupted at the monocyclic stage. These mono- and bicyclic structures support our hypothesis of a two-stage reaction sequence leading to penicillin. Furthermore, the formation of a monocyclic sulphoxide product from ACmC is most simply explained by the interception of a high-valency iron-oxo species.
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==About this Structure==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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1QJE 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=1QJE OCA].
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</div>
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<div class="pdbe-citations 1qje" style="background-color:#fffaf0;"></div>
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==Reference==
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==See Also==
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The reaction cycle of isopenicillin N synthase observed by X-ray diffraction., Burzlaff NI, Rutledge PJ, Clifton IJ, Hensgens CM, Pickford M, Adlington RM, Roach PL, Baldwin JE, Nature. 1999 Oct 14;401(6754):721-4. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/10537113 10537113]
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*[[Isopenicillin N synthase|Isopenicillin N synthase]]
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[[Category: Emericella nidulans]]
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== References ==
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[[Category: Single protein]]
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<references/>
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[[Category: Adlington, R M.]]
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__TOC__
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[[Category: Baldwin, J E.]]
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</StructureSection>
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[[Category: Burzlaff, N I.]]
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[[Category: Aspergillus nidulans]]
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[[Category: Clifton, I J.]]
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[[Category: Large Structures]]
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[[Category: Roach, P L.]]
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[[Category: Adlington RM]]
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[[Category: Rutledge, P J.]]
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[[Category: Baldwin JE]]
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[[Category: B-lactam antibiotic]]
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[[Category: Burzlaff NI]]
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[[Category: Enzyme-product complex]]
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[[Category: Clifton IJ]]
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[[Category: Oxygenase]]
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[[Category: Roach PL]]
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[[Category: Penicillin biosynthesis]]
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[[Category: Rutledge PJ]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 06:20:47 2008''
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Current revision

Isopenicillin N synthase from Aspergillus nidulans (IP1 - Fe complex)

PDB ID 1qje

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