4bb3: Difference between revisions

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-{{STRUCTURE_4bb3|  PDB=4bb3  |  SCENE=  }}
-===Isopenicillin N synthase with the dipeptide substrate analogue AhC===
-{{ABSTRACT_PUBMED_23262315}}
-==Function==
+==Isopenicillin N synthase with the dipeptide substrate analogue AhC==
-[[http://www.uniprot.org/uniprot/IPNS_EMENI IPNS_EMENI]] Removes, in the presence of oxygen, 4 hydrogen atoms from delta-L-(alpha-aminoadipyl)-L-cysteinyl-D-valine (ACV) to form the azetidinone and thiazolidine rings of isopenicillin.
+<StructureSection load='4bb3' size='340' side='right'caption='[[4bb3]], [[Resolution|resolution]] 1.40&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[4bb3]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Aspergillus_nidulans_FGSC_A4 Aspergillus nidulans FGSC A4]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4BB3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4BB3 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]] 1.4&#8491;</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=KKA:(2S)-2-AZANYL-6-OXIDANYLIDENE-6-[[(2S)-1-OXIDANYL-1-OXIDANYLIDENE-4-SULFANYL-BUTAN-2-YL]AMINO]HEXANOIC+ACID'>KKA</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=4bb3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4bb3 OCA], [https://pdbe.org/4bb3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4bb3 RCSB], [https://www.ebi.ac.uk/pdbsum/4bb3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4bb3 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>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Isopenicillin N synthase (IPNS) converts its linear tripeptide substrate delta-L-alpha-aminoadipoyl-L-cysteinyl-D-valine (ACV) to bicyclic isopenicillin N (IPN), the key step in penicillin biosynthesis. Solution-phase incubation experiments have shown that IPNS will accept and oxidise a diverse array of substrate analogues, including tripeptides that incorporate L-homocysteine as their second residue, and tripeptides with truncated side-chains at the third amino acid such as delta-L-alpha-aminoadipoyl-L-cysteinyl-D-alpha-aminobutyrate (ACAb), delta-L-alpha-aminoadipoyl-L-cysteinyl-D-alanine (ACA) and delta-L-alpha-aminoadipoyl-L-cysteinyl-glycine (ACG). However IPNS does not react with dipeptide substrates. To probe this selectivity we have crystallised the enzyme with the dipeptide delta-L-alpha-aminoadipoyl-L-homocysteine (AhC) and solved a crystal structure for the IPNS:Fe(II):AhC complex to 1.40 A resolution. This structure reveals an unexpected mode of peptide binding at the IPNS active site, in which the homocysteinyl thiolate does not bind to iron. Instead the primary mode of binding sees the homocysteinyl carboxylate coordinated to the metal, while its side-chain is oriented into the region of the active site normally occupied by the benzyl group of protein residue Phe211.
-==About this Structure==
+The crystal structure of isopenicillin N synthase with a dipeptide substrate analogue.,Daruzzaman A, Clifton IJ, Adlington RM, Baldwin JE, Rutledge PJ Arch Biochem Biophys. 2013 Feb 1;530(1):48-53. doi: 10.1016/j.abb.2012.12.012., Epub 2012 Dec 19. PMID:23262315<ref>PMID:23262315</ref>
-[[4bb3]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Aspergillus_nidulans_fgsc_a4 Aspergillus nidulans fgsc a4]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4BB3 OCA].
-[[Category: Aspergillus nidulans fgsc a4]]
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Isopenicillin-N synthase]]
+</div>
-[[Category: Clifton, I J.]]
+<div class="pdbe-citations 4bb3" style="background-color:#fffaf0;"></div>
-[[Category: Daruzzaman, A.]]
-[[Category: Rutledge, P J.]]
+==See Also==
-[[Category: Antibiotic biosynthesis]]
+*[[Isopenicillin N synthase|Isopenicillin N synthase]]
-[[Category: B-lactam antibiotic]]
+== References ==
-[[Category: Oxidoreductase]]
+<references/>
-[[Category: Oxygenase]]
+__TOC__
-[[Category: Penicillin biosynthesis]]
+</StructureSection>
+[[Category: Aspergillus nidulans FGSC A4]]
+[[Category: Large Structures]]
+[[Category: Clifton IJ]]
+[[Category: Daruzzaman A]]
+[[Category: Rutledge PJ]]