View source for 6zaf


==Room temperature XFEL Isopenicillin N synthase structure in complex with Fe and ACV after exposure to dioxygen for 400ms.==
<StructureSection load='6zaf' size='340' side='right'caption='[[6zaf]], [[Resolution|resolution]] 1.40&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6zaf]] 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=6ZAF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6ZAF 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]] 1.4001&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACV:L-D-(A-AMINOADIPOYL)-L-CYSTEINYL-D-VALINE'>ACV</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=6zaf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6zaf OCA], [https://pdbe.org/6zaf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6zaf RCSB], [https://www.ebi.ac.uk/pdbsum/6zaf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6zaf 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) catalyzes the unique reaction of l-delta-(alpha-aminoadipoyl)-l-cysteinyl-d-valine (ACV) with dioxygen giving isopenicillin N (IPN), the precursor of all natural penicillins and cephalosporins. X-ray free-electron laser studies including time-resolved crystallography and emission spectroscopy reveal how reaction of IPNS:Fe(II):ACV with dioxygen to yield an Fe(III) superoxide causes differences in active site volume and unexpected conformational changes that propagate to structurally remote regions. Combined with solution studies, the results reveal the importance of protein dynamics in regulating intermediate conformations during conversion of ACV to IPN. The results have implications for catalysis by multiple IPNS-related oxygenases, including those involved in the human hypoxic response, and highlight the power of serial femtosecond crystallography to provide insight into long-range enzyme dynamics during reactions presently impossible for nonprotein catalysts.

X-ray free-electron laser studies reveal correlated motion during isopenicillin N synthase catalysis.,Rabe P, Kamps JJAG, Sutherlin KD, Linyard JDS, Aller P, Pham CC, Makita H, Clifton I, McDonough MA, Leissing TM, Shutin D, Lang PA, Butryn A, Brem J, Gul S, Fuller FD, Kim IS, Cheah MH, Fransson T, Bhowmick A, Young ID, O'Riordan L, Brewster AS, Pettinati I, Doyle M, Joti Y, Owada S, Tono K, Batyuk A, Hunter MS, Alonso-Mori R, Bergmann U, Owen RL, Sauter NK, Claridge TDW, Robinson CV, Yachandra VK, Yano J, Kern JF, Orville AM, Schofield CJ Sci Adv. 2021 Aug 20;7(34):eabh0250. doi: 10.1126/sciadv.abh0250. Print 2021 Aug. PMID:34417180<ref>PMID:34417180</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6zaf" style="background-color:#fffaf0;"></div>

==See Also==
*[[Isopenicillin N synthase|Isopenicillin N synthase]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Aspergillus nidulans FGSC A4]]
[[Category: Large Structures]]
[[Category: Aller P]]
[[Category: Alonso-Mori R]]
[[Category: Batyuk A]]
[[Category: Bhowmick A]]
[[Category: Brem J]]
[[Category: Brewster AS]]
[[Category: Butryn A]]
[[Category: Claridge TDW]]
[[Category: Clifton IJ]]
[[Category: Fuller FD]]
[[Category: Gul S]]
[[Category: Hunter MS]]
[[Category: Kamps JJAG]]
[[Category: Kern JF]]
[[Category: Kim I]]
[[Category: Lang P]]
[[Category: Leissing TM]]
[[Category: Linyard J]]
[[Category: McDonough MA]]
[[Category: ORiordan L]]
[[Category: Orville AM]]
[[Category: Pettinati I]]
[[Category: Pharm C]]
[[Category: Rabe P]]
[[Category: Sauter NK]]
[[Category: Schofield CJ]]
[[Category: Sutherlin K]]
[[Category: Yachandra V]]
[[Category: Yano J]]
[[Category: Young I]]