View source for 1odm


==ISOPENICILLIN N SYNTHASE FROM ASPERGILLUS NIDULANS (ANAEROBIC AC-VINYLGLYCINE FE COMPLEX)==
<StructureSection load='1odm' size='340' side='right'caption='[[1odm]], [[Resolution|resolution]] 1.15&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1odm]] 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=1ODM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1ODM FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.15&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ASV:DELTA-(L-ALPHA-AMINOADIPOYL)-L-CYSTEINYL-D-VINYLGLYCINE'>ASV</scene>, <scene name='pdbligand=FE2:FE+(II)+ION'>FE2</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1odm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1odm OCA], [https://pdbe.org/1odm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1odm RCSB], [https://www.ebi.ac.uk/pdbsum/1odm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1odm ProSAT]</span></td></tr>
</table>
== Function ==
[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> 
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/od/1odm_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</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=1odm ConSurf].
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== Publication Abstract from PubMed ==
Isopenicillin N synthase (IPNS) catalyses conversion of the linear tripeptide delta-(L-alpha-aminoadipoyl)-L-cysteinyl-D-valine (ACV) to isopenicillin N (IPN), the central step in biosynthesis of the beta-lactam antibiotics. The unsaturated substrate analogue delta-(L-alpha-aminoadipoyl)-L-cysteinyl-D-vinylglycine (ACvG) has previously been incubated with IPNS and single product was isolated, a 2-alpha-hydroxymethyl isopenicillin N (HMPen), formed via a monooxygenase mode of reactivity. ACvG has now been crystallised with IPNS and the structure of the anaerobic IPNS:Fe(II):ACvG complex determined to 1.15 A resolution. Furthermore, by exposing the anaerobically grown crystals to high-pressure oxygen gas, a structure corresponding to the bicyclic product HMPen has been obtained at 1.60 A resolution. In light of these and other IPNS structures, and recent developments with related dioxygenases, the [2 + 2] cycloaddition mechanism for HMPen formation from ACvG has been revised, and a stepwise radical mechanism is proposed. This revised mechanism remains consistent with the observed stereospecificity of the transformation, but fits better with apparent constraints on the coordination geometry around the active site iron atom.

Crystallographic studies on the reaction of isopenicillin N synthase with an unsaturated substrate analogue.,Elkins JM, Rutledge PJ, Burzlaff NI, Clifton IJ, Adlington RM, Roach PL, Baldwin JE Org Biomol Chem. 2003 May 7;1(9):1455-60. PMID:12926272<ref>PMID:12926272</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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==See Also==
*[[Isopenicillin N synthase|Isopenicillin N synthase]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Aspergillus nidulans]]
[[Category: Large Structures]]
[[Category: Adlington RM]]
[[Category: Baldwin JE]]
[[Category: Burzlaff NI]]
[[Category: Clifton IJ]]
[[Category: Elkins JM]]
[[Category: Roach PL]]
[[Category: Rutledge PJ]]