2y60: Difference between revisions
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< | ==Isopenicillin N synthase with AC-D-methionine== | ||
<StructureSection load='2y60' size='340' side='right'caption='[[2y60]], [[Resolution|resolution]] 1.40Å' scene=''> | |||
== Structural highlights == | |||
or the | <table><tr><td colspan='2'>[[2y60]] 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=2Y60 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2Y60 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]] 1.4Å</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=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=M8F:N-[(5S)-5-AMINO-5-CARBOXYPENTANOYL]-L-CYSTEINYL-D-METHIONINE'>M8F</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=2y60 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2y60 OCA], [https://pdbe.org/2y60 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2y60 RCSB], [https://www.ebi.ac.uk/pdbsum/2y60 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2y60 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) catalyses cyclization of delta-(l-alpha-aminoadipoyl)-l-cysteinyl-d-valine (ACV) to isopenicillin N (IPN), the central step in penicillin biosynthesis. Previous studies have shown that IPNS turns over a wide range of substrate analogues in which the valine residue of its natural substrate is replaced with other amino acids. IPNS accepts and oxidizes numerous substrates that bear hydrocarbon sidechains in this position, however the enzyme is less tolerant of analogues presenting polar functionality in place of the valinyl isopropyl group. We report a new ACV analogue delta-(l-alpha-aminoadipoyl)-l-cysteinyl-d-methionine (ACM), which incorporates a thioether in place of the valinyl sidechain. ACM has been synthesized using solution phase methods and crystallized with IPNS. A crystal structure has been elucidated for the IPNS:Fe(II):ACM complex at 1.40A resolution. This structure reveals that ACM binds in the IPNS active site such that the sulfur atom of the methionine thioether binds to iron in the oxygen binding site at a distance of 2.57A. The sulfur of the cysteinyl thiolate sits 2.36A from the metal. | |||
The crystal structure of isopenicillin N synthase with delta-((L)-alpha-aminoadipoyl)-(L)-cysteinyl-(D)-methionine reveals thioether coordination to iron.,Clifton IJ, Ge W, Adlington RM, Baldwin JE, Rutledge PJ Arch Biochem Biophys. 2011 Dec 15;516(2):103-7. doi: 10.1016/j.abb.2011.09.014., Epub 2011 Oct 6. PMID:22001738<ref>PMID:22001738</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 2y60" style="background-color:#fffaf0;"></div> | |||
== | ==See Also== | ||
[[ | *[[Isopenicillin N synthase|Isopenicillin N synthase]] | ||
[[Category: | == References == | ||
[[Category: | <references/> | ||
[[Category: Clifton | __TOC__ | ||
[[Category: Ge | </StructureSection> | ||
[[Category: Rutledge | [[Category: Aspergillus nidulans]] | ||
[[Category: Large Structures]] | |||
[[Category: Clifton IJ]] | |||
[[Category: Ge W]] | |||
[[Category: Rutledge PJ]] | |||
Latest revision as of 11:08, 23 August 2023
Isopenicillin N synthase with AC-D-methionineIsopenicillin N synthase with AC-D-methionine
Structural highlights
FunctionIPNA_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][1] [2] [3] Publication Abstract from PubMedIsopenicillin N synthase (IPNS) catalyses cyclization of delta-(l-alpha-aminoadipoyl)-l-cysteinyl-d-valine (ACV) to isopenicillin N (IPN), the central step in penicillin biosynthesis. Previous studies have shown that IPNS turns over a wide range of substrate analogues in which the valine residue of its natural substrate is replaced with other amino acids. IPNS accepts and oxidizes numerous substrates that bear hydrocarbon sidechains in this position, however the enzyme is less tolerant of analogues presenting polar functionality in place of the valinyl isopropyl group. We report a new ACV analogue delta-(l-alpha-aminoadipoyl)-l-cysteinyl-d-methionine (ACM), which incorporates a thioether in place of the valinyl sidechain. ACM has been synthesized using solution phase methods and crystallized with IPNS. A crystal structure has been elucidated for the IPNS:Fe(II):ACM complex at 1.40A resolution. This structure reveals that ACM binds in the IPNS active site such that the sulfur atom of the methionine thioether binds to iron in the oxygen binding site at a distance of 2.57A. The sulfur of the cysteinyl thiolate sits 2.36A from the metal. The crystal structure of isopenicillin N synthase with delta-((L)-alpha-aminoadipoyl)-(L)-cysteinyl-(D)-methionine reveals thioether coordination to iron.,Clifton IJ, Ge W, Adlington RM, Baldwin JE, Rutledge PJ Arch Biochem Biophys. 2011 Dec 15;516(2):103-7. doi: 10.1016/j.abb.2011.09.014., Epub 2011 Oct 6. PMID:22001738[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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