2jb4: Difference between revisions

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-[[Image:2jb4.gif|left|200px]]
-<!--
-The line below this paragraph, containing "STRUCTURE_2jb4", creates the "Structure Box" on the page.
-You may change the PDB parameter (which sets the PDB file loaded into the applet)
-or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-or leave the SCENE parameter empty for the default display.
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-{{STRUCTURE_2jb4|  PDB=2jb4  |  SCENE=  }}
-'''ISOPENICILLIN N SYNTHASE WITH A 2-THIABICYCLOHEPTAN-6-ONE PRODUCT ANALOGUE'''
+==Isopenicillin N synthase with a 2-thiabicycloheptan-6-one product analogue==
+<StructureSection load='2jb4' size='340' side='right'caption='[[2jb4]], [[Resolution|resolution]] 1.30&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[2jb4]] 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=2JB4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2JB4 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]] 1.3&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A14:(1S,4S,5S,7R)-7-{[(5S)-5-AMINO-5-CARBOXYPENTANOYL]AMINO}-3,3-DIMETHYL-6-OXO-2-THIABICYCLO[3.2.0]HEPTANE-4-CARBOXYLIC+ACID'>A14</scene>, <scene name='pdbligand=FE:FE+(III)+ION'>FE</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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=2jb4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2jb4 OCA], [https://pdbe.org/2jb4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2jb4 RCSB], [https://www.ebi.ac.uk/pdbsum/2jb4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2jb4 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/jb/2jb4_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=2jb4 ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+A carbocyclic analogue of the beta-lactam antibiotic isopenicillin N (IPN) has been synthesised and cocrystallised with isopenicillin N synthase (IPNS), the central enzyme in the biosynthesis of penicillin antibiotics. The crystal structure of the IPNS-cyclobutanone complex reveals an active site environment similar to that seen in the enzyme-product complex generated by turnover of the natural substrate within the crystalline protein. The IPNS-cyclobutanone structure demonstrates that the product analogue is tethered to the protein by hydrogen bonding and salt bridge interactions with its carboxylate groups, as seen previously for the natural substrate and product. Furthermore, the successful cocrystallisation of this analogue with IPNS provides firm structural evidence for the utility of such cyclobutanone derivatives as hydrolytically stable analogues of bicyclic beta-lactams.
-==Overview==
+A cyclobutanone analogue mimics penicillin in binding to isopenicillin N synthase.,Stewart AC, Clifton IJ, Adlington RM, Baldwin JE, Rutledge PJ Chembiochem. 2007 Nov 5;8(16):2003-7. PMID:17907118<ref>PMID:17907118</ref>
-A carbocyclic analogue of the beta-lactam antibiotic isopenicillin N (IPN) has been synthesised and cocrystallised with isopenicillin N synthase (IPNS), the central enzyme in the biosynthesis of penicillin antibiotics. The crystal structure of the IPNS-cyclobutanone complex reveals an active site environment similar to that seen in the enzyme-product complex generated by turnover of the natural substrate within the crystalline protein. The IPNS-cyclobutanone structure demonstrates that the product analogue is tethered to the protein by hydrogen bonding and salt bridge interactions with its carboxylate groups, as seen previously for the natural substrate and product. Furthermore, the successful cocrystallisation of this analogue with IPNS provides firm structural evidence for the utility of such cyclobutanone derivatives as hydrolytically stable analogues of bicyclic beta-lactams.
-==About this Structure==
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-JB4 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Emericella_nidulans Emericella nidulans]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2JB4 OCA].
+</div>
+<div class="pdbe-citations 2jb4" style="background-color:#fffaf0;"></div>
-==Reference==
+==See Also==
-A cyclobutanone analogue mimics penicillin in binding to isopenicillin N synthase., Stewart AC, Clifton IJ, Adlington RM, Baldwin JE, Rutledge PJ, Chembiochem. 2007 Nov 5;8(16):2003-7. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/17907118 17907118]
+*[[Isopenicillin N synthase|Isopenicillin N synthase]]
-[[Category: Emericella nidulans]]
+== References ==
-[[Category: Isopenicillin-N synthase]]
+<references/>
-[[Category: Single protein]]
+__TOC__
-[[Category: Adlington, R M.]]
+</StructureSection>
-[[Category: Baldwin, J E.]]
+[[Category: Aspergillus nidulans]]
-[[Category: Clifton, I J.]]
+[[Category: Large Structures]]
-[[Category: Rutledge, P J.]]
+[[Category: Adlington RM]]
-[[Category: Stewart, A C.]]
+[[Category: Baldwin JE]]
-[[Category: Antibiotic biosynthesis]]
+[[Category: Clifton IJ]]
-[[Category: B-lactam antibiotic]]
+[[Category: Rutledge PJ]]
-[[Category: Iron]]
+[[Category: Stewart AC]]
-[[Category: Metal-binding]]
-[[Category: Oxidoreductase]]
-[[Category: Oxygenase]]
-[[Category: Penicillin biosynthesis]]
-[[Category: Vitamin c]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May  4 08:38:06 2008''