This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.

Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.

3zoi

From Proteopedia

(Difference between revisions)

Jump to: navigation, search

Current revision

ISOPENICILLIN N SYNTHASE WITH AC-O-METHYL-D-THREONINE

Structural highlights

3zoi is a 1 chain structure with sequence from Aspergillus nidulans. This structure supersedes the now removed PDB entry 2y86. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.82Å
Ligands:	, , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

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]^[1] ^[2] ^[3]

Publication Abstract from PubMed

Isopenicillin N synthase (IPNS) is a non-heme iron oxidase central to the biosynthesis of beta-lactam antibiotics. IPNS converts the tripeptide delta-(L-alpha-aminoadipoyl)-L-cysteinyl-D-valine (ACV) to isopenicillin N while reducing molecular oxygen to water. The substrate analogue delta-(L-alpha-aminoadipoyl)-L-cysteinyl-O-methyl-D-threonine (ACmT) is not turned over by IPNS. Epimeric delta-(L-alpha-aminoadipoyl)-L-cysteinyl-O-methyl-D-allo-threonine (ACmaT) is converted to a bioactive penam product. ACmT and ACmaT differ from each other only in the stereochemistry at the beta-carbon atom of their third residue. These substrates both contain a methyl ether in place of the isopropyl group of ACV. We report an X-ray crystal structure for the anaerobic IPNS:Fe(II):ACmT complex. This structure reveals an additional water molecule bound to the active site metal, held by hydrogen-bonding to the ether oxygen atom of the substrate analogue.

The crystal structure of an isopenicillin N synthase complex with an ethereal substrate analogue reveals water in the oxygen binding site.,Clifton IJ, Ge W, Adlington RM, Baldwin JE, Rutledge PJ FEBS Lett. 2013 Aug 19;587(16):2705-9. doi: 10.1016/j.febslet.2013.07.016. Epub, 2013 Jul 13. PMID:23860486^[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Ogle JM, Clifton IJ, Rutledge PJ, Elkins JM, Burzlaff NI, Adlington RM, Roach PL, Baldwin JE. Alternative oxidation by isopenicillin N synthase observed by X-ray diffraction. Chem Biol. 2001 Dec;8(12):1231-7. PMID:11755401
↑ McNeill LA, Brown TJN, Sami M, Clifton IJ, Burzlaff NI, Claridge TDW, Adlington RM, Baldwin JE, Rutledge PJ, Schofield CJ. Terminally Truncated Isopenicillin N Synthase Generates a Dithioester Product: Evidence for a Thioaldehyde Intermediate during Catalysis and a New Mode of Reaction for Non-Heme Iron Oxidases. Chemistry. 2017 Sep 18;23(52):12815-12824. doi: 10.1002/chem.201701592. Epub 2017, Aug 21. PMID:28703303 doi:http://dx.doi.org/10.1002/chem.201701592
↑ Ramon D, Carramolino L, Patino C, Sanchez F, Penalva MA. Cloning and characterization of the isopenicillin N synthetase gene mediating the formation of the beta-lactam ring in Aspergillus nidulans. Gene. 1987;57(2-3):171-81. doi: 10.1016/0378-1119(87)90120-x. PMID:3319778 doi:http://dx.doi.org/10.1016/0378-1119(87)90120-x
↑ Clifton IJ, Ge W, Adlington RM, Baldwin JE, Rutledge PJ. The crystal structure of an isopenicillin N synthase complex with an ethereal substrate analogue reveals water in the oxygen binding site. FEBS Lett. 2013 Aug 19;587(16):2705-9. doi: 10.1016/j.febslet.2013.07.016. Epub, 2013 Jul 13. PMID:23860486 doi:http://dx.doi.org/10.1016/j.febslet.2013.07.016

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3zoi"

Categories: Aspergillus nidulans | Large Structures | Clifton IJ | Ge W | Rutledge PJ

@@ Line 1: / Line 1: @@
 ==ISOPENICILLIN N SYNTHASE WITH AC-O-METHYL-D-THREONINE==
-<StructureSection load='3zoi' size='340' side='right' caption='[[3zoi]], [[Resolution|resolution]] 1.82&Aring;' scene=''>
+<StructureSection load='3zoi' size='340' side='right'caption='[[3zoi]], [[Resolution|resolution]] 1.82&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3zoi]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/A._nidulans A. nidulans]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=2y86 2y86]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3ZOI OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3ZOI FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3zoi]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Aspergillus_nidulans Aspergillus nidulans]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=2y86 2y86]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3ZOI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3ZOI FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FE:FE+(III)+ION'>FE</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=M2W:DELTA-(L-ALPHA-AMINOADIPOYL)-L-CYSTEINYL-O-METHYL-D-THREONINE'>M2W</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.82&#8491;</td></tr>
-<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Isopenicillin-N_synthase Isopenicillin-N synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.21.3.1 1.21.3.1] </span></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=M2W:DELTA-(L-ALPHA-AMINOADIPOYL)-L-CYSTEINYL-O-METHYL-D-THREONINE'>M2W</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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3zoi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3zoi OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3zoi RCSB], [http://www.ebi.ac.uk/pdbsum/3zoi PDBsum]</span></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=3zoi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3zoi OCA], [https://pdbe.org/3zoi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3zoi RCSB], [https://www.ebi.ac.uk/pdbsum/3zoi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3zoi ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[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.
+[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 ==
@@ Line 17: / Line 18: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 3zoi" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Isopenicillin N synthase|Isopenicillin N synthase]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: A. nidulans]]
+[[Category: Aspergillus nidulans]]
-[[Category: Isopenicillin-N synthase]]
+[[Category: Large Structures]]
-[[Category: Clifton, I J]]
+[[Category: Clifton IJ]]
-[[Category: Ge, W]]
+[[Category: Ge W]]
-[[Category: Rutledge, P J]]
+[[Category: Rutledge PJ]]
-[[Category: B-lactam antibiotic]]
-[[Category: Oxidoreductase]]
-[[Category: Oxygenase]]
-[[Category: Penicillin biosynthesis]]

3zoi

From Proteopedia

Current revision

ISOPENICILLIN N SYNTHASE WITH AC-O-METHYL-D-THREONINE

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox