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1qiq

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(New page: 200px<br /> <applet load="1qiq" size="450" color="white" frame="true" align="right" spinBox="true" caption="1qiq, resolution 1.5&Aring;" /> '''ISOPENICILLIN N SYNT...)
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[[Image:1qiq.gif|left|200px]]<br />
 
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<applet load="1qiq" size="450" color="white" frame="true" align="right" spinBox="true"
 
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caption="1qiq, resolution 1.5&Aring;" />
 
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'''ISOPENICILLIN N SYNTHASE FROM ASPERGILLUS NIDULANS (ACMC FE COMPLEX)'''<br />
 
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==Overview==
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==ISOPENICILLIN N SYNTHASE FROM ASPERGILLUS NIDULANS (ACmC Fe COMPLEX)==
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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 ... [[http://ispc.weizmann.ac.il/pmbin/getpm?10537113 (full description)]]
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<StructureSection load='1qiq' size='340' side='right'caption='[[1qiq]], [[Resolution|resolution]] 1.50&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1qiq]] 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=1QIQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1QIQ FirstGlance]. <br>
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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]] 1.5&#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=ACC:N-[N-[2-AMINO-6-OXO-HEXANOIC+ACID-6-YL]CYSTEINYL]-S-METHYLCYSTEINE'>ACC</scene>, <scene name='pdbligand=FE:FE+(III)+ION'>FE</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
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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=1qiq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1qiq OCA], [https://pdbe.org/1qiq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1qiq RCSB], [https://www.ebi.ac.uk/pdbsum/1qiq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1qiq 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/qi/1qiq_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=1qiq 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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==About this Structure==
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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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1QIQ 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 FE, SO4 and ACC as [[http://en.wikipedia.org/wiki/ligands ligands]]. Full crystallographic information is available from [[http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1QIQ OCA]].
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==Reference==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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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://ispc.weizmann.ac.il//pmbin/getpm?pmid=10537113 10537113]
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</div>
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[[Category: Emericella nidulans]]
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<div class="pdbe-citations 1qiq" style="background-color:#fffaf0;"></div>
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[[Category: Single protein]]
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[[Category: Adlington, R.M.]]
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[[Category: Baldwin, J.E.]]
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[[Category: Burzlaff, N.]]
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[[Category: Clifton, I.J.]]
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[[Category: Roach, P.L.]]
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[[Category: Rutledge, P.J.]]
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[[Category: ACC]]
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[[Category: FE]]
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[[Category: SO4]]
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[[Category: b-lactam antibiotic]]
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[[Category: monocyclic intermediate]]
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[[Category: oxygenase]]
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[[Category: penicillin biosynthesis]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Oct 29 21:29:22 2007''
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==See Also==
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*[[Isopenicillin N synthase|Isopenicillin N synthase]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
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[[Category: Aspergillus nidulans]]
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[[Category: Large Structures]]
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[[Category: Adlington RM]]
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[[Category: Baldwin JE]]
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[[Category: Burzlaff NI]]
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[[Category: Clifton IJ]]
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[[Category: Roach PL]]
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[[Category: Rutledge PJ]]

Current revision

ISOPENICILLIN N SYNTHASE FROM ASPERGILLUS NIDULANS (ACmC Fe COMPLEX)

PDB ID 1qiq

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