2ivj: Difference between revisions
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== | ==Isopenicillin N Synthase From Aspergillus Nidulans (Anaerobic Ac- cyclopropylglycine Fe Complex)== | ||
[[2ivj]] is a 1 chain structure with sequence from [ | <StructureSection load='2ivj' size='340' side='right'caption='[[2ivj]], [[Resolution|resolution]] 1.46Å' scene=''> | ||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[2ivj]] 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=2IVJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2IVJ 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]] 1.46Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BCV:D-(L-A-AMINOADIPOYL)-L-CYSTEINYL-D-CYCLOPROPYLGLYCINE'>BCV</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=2ivj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ivj OCA], [https://pdbe.org/2ivj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2ivj RCSB], [https://www.ebi.ac.uk/pdbsum/2ivj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2ivj 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/iv/2ivj_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=2ivj ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Isopenicillin N synthase (IPNS), a non-heme iron oxidase central to penicillin and cephalosporin biosynthesis, catalyzes an energetically demanding chemical transformation to produce isopenicillin N from the tripeptide delta-(l-alpha-aminoadipoyl)-l-cysteinyl-d-valine (ACV). We describe the synthesis of two cyclopropyl-containing tripeptide analogues, delta-(l-alpha-aminoadipoyl)-l-cysteinyl-beta-methyl-d-cyclopropylglycine and delta-(l-alpha-aminoadipoyl)-l-cysteinyl-d-cyclopropylglycine, designed as probes for the mechanism of IPNS. We have solved the X-ray crystal structures of these substrates in complex with IPNS and propose a revised mechanism for the IPNS-mediated turnover of these compounds. Relative to the previously determined IPNS-Fe(II)-ACV structure, key differences exist in substrate orientation and water occupancy, which allow for an explanation of the differences in reactivity of these substrates. | |||
Interactions of isopenicillin N synthase with cyclopropyl-containing substrate analogues reveal new mechanistic insight.,Howard-Jones AR, Elkins JM, Clifton IJ, Roach PL, Adlington RM, Baldwin JE, Rutledge PJ Biochemistry. 2007 Apr 24;46(16):4755-62. Epub 2007 Mar 31. PMID:17397141<ref>PMID:17397141</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 2ivj" 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: Elkins | [[Category: Clifton IJ]] | ||
[[Category: Howard-Jones | [[Category: Elkins JM]] | ||
[[Category: Roach | [[Category: Howard-Jones AR]] | ||
[[Category: Rutledge | [[Category: Roach PL]] | ||
[[Category: Rutledge PJ]] | |||
