2bu9
From Proteopedia
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| - | [[Image:2bu9.png|left|200px]] | ||
| - | + | ==Isopenicillin N synthase complexed with L-aminoadipoyl-L-cysteinyl-L- hexafluorovaline== | |
| + | <StructureSection load='2bu9' size='340' side='right'caption='[[2bu9]], [[Resolution|resolution]] 1.30Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[2bu9]] 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=2BU9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2BU9 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]] 1.3Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FE:FE+(III)+ION'>FE</scene>, <scene name='pdbligand=HFV:DELTA-(L-ALPHA-AMINOADIPOYL)-L-CYSTEINYL-L-3,3,3,3,3,3-HEXAFLUOROVALINE'>HFV</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=2bu9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2bu9 OCA], [https://pdbe.org/2bu9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2bu9 RCSB], [https://www.ebi.ac.uk/pdbsum/2bu9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2bu9 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/bu/2bu9_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=2bu9 ConSurf]. | ||
| + | <div style="clear:both"></div> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Isopenicillin N synthase (IPNS) is a non-haem iron oxidase that catalyses the formation of isopenicillin N from the tripeptide delta-(L-alpha-aminoadipoyl)-L-cysteinyl-D-valine. In this report, we describe the crystal structure of the enzyme with a non-natural L,L,L-tripeptide substrate, delta-(L-alpha-aminoadipoyl)-L-cysteinyl-L-3,3,3,3',3',3'-hexafluorovaline . This structure reveals a strong binding interaction of the tripeptide within the active site and a unique conformation for the non-natural L,L,L-diastereomer. Taken together, these findings provide a possible rationale for the previously observed inhibitory effects of L,L,L-tripeptide substrates on IPNS activity. | ||
| - | + | Unique binding of a non-natural L,L,L-substrate by isopenicillin N synthase.,Howard-Jones AR, Rutledge PJ, Clifton IJ, Adlington RM, Baldwin JE Biochem Biophys Res Commun. 2005 Oct 21;336(2):702-8. PMID:16143309<ref>PMID:16143309</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| - | + | <div class="pdbe-citations 2bu9" style="background-color:#fffaf0;"></div> | |
| - | + | ||
==See Also== | ==See Also== | ||
*[[Isopenicillin N synthase|Isopenicillin N synthase]] | *[[Isopenicillin N synthase|Isopenicillin N synthase]] | ||
| - | + | == References == | |
| - | == | + | <references/> |
| - | < | + | __TOC__ |
| - | [[Category: | + | </StructureSection> |
| - | [[Category: | + | [[Category: Aspergillus nidulans]] |
| - | [[Category: Adlington | + | [[Category: Large Structures]] |
| - | [[Category: Baldwin | + | [[Category: Adlington RM]] |
| - | [[Category: Clifton | + | [[Category: Baldwin JE]] |
| - | [[Category: Howard-Jones | + | [[Category: Clifton IJ]] |
| - | [[Category: Rutledge | + | [[Category: Howard-Jones AR]] |
| - | + | [[Category: Rutledge PJ]] | |
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Current revision
Isopenicillin N synthase complexed with L-aminoadipoyl-L-cysteinyl-L- hexafluorovaline
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