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| | <StructureSection load='3zku' size='340' side='right'caption='[[3zku]], [[Resolution|resolution]] 1.40Å' scene=''> | | <StructureSection load='3zku' size='340' side='right'caption='[[3zku]], [[Resolution|resolution]] 1.40Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3zku]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/A._nidulans A. nidulans]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3ZKU OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3ZKU FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3zku]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/A._nidulans A. nidulans]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3ZKU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3ZKU 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=HCV:N-[(5S)-5-AMINO-5-CARBOXYPENTANOYL]-L-HOMOCYSTEYL-D-VALINE'>HCV</scene></td></tr> | + | </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=HCV:N-[(5S)-5-AMINO-5-CARBOXYPENTANOYL]-L-HOMOCYSTEYL-D-VALINE'>HCV</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3zky|3zky]]</td></tr> | + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3zky|3zky]]</div></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='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Isopenicillin-N_synthase Isopenicillin-N synthase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.21.3.1 1.21.3.1] </span></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=3zku FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3zku OCA], [http://pdbe.org/3zku PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3zku RCSB], [http://www.ebi.ac.uk/pdbsum/3zku PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3zku ProSAT]</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=3zku FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3zku OCA], [https://pdbe.org/3zku PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3zku RCSB], [https://www.ebi.ac.uk/pdbsum/3zku PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3zku ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == 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/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. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
| Structural highlights
Function
[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.
Publication Abstract from PubMed
Isopenicillin N synthase (IPNS) converts the linear tripeptide delta-(L-alpha-aminoadipoyl)-L-cysteinyl-D-valine (ACV) into bicyclic isopenicillin N (IPN) in the central step in the biosynthesis of penicillin and cephalosporin antibiotics. Solution-phase incubation experiments have shown that IPNS turns over analogues with a diverse range of side chains in the third (valinyl) position of the substrate, but copes less well with changes in the second (cysteinyl) residue. IPNS thus converts the homologated tripeptides delta-(L-alpha-aminoadipoyl)-L-homocysteinyl-D-valine (AhCV) and delta-(L-alpha-aminoadipoyl)-L-homocysteinyl-D-allylglycine (AhCaG) into monocyclic hydroxy-lactam products; this suggests that the additional methylene unit in these substrates induces conformational changes that preclude second ring closure after initial lactam formation. To investigate this and solution-phase results with other tripeptides delta-(L-alpha-aminoadipoyl)-L-homocysteinyl-D-Xaa, we have crystallised AhCV and delta-(L-alpha-aminoadipoyl)-L-homocysteinyl-D-S-methylcysteine (AhCmC) with IPNS and solved crystal structures for the resulting complexes. The IPNS:Fe :AhCV complex shows diffuse electron density for several regions of the substrate, revealing considerable conformational freedom within the active site. The substrate is more clearly resolved in the IPNS:Fe :AhCmC complex, by virtue of thioether coordination to iron. AhCmC occupies two distinct conformations, both distorted relative to the natural substrate ACV, in order to accommodate the extra methylene group in the second residue. Attempts to turn these substrates over within crystalline IPNS using hyperbaric oxygenation give rise to product mixtures.
The Interaction of Isopenicillin N Synthase with Homologated Substrate Analogues delta-(L-alpha-Aminoadipoyl)-L-homocysteinyl-D-Xaa Characterised by Protein Crystallography.,Daruzzaman A, Clifton IJ, Adlington RM, Baldwin JE, Rutledge PJ Chembiochem. 2013 Mar 18;14(5):599-606. doi: 10.1002/cbic.201200728. Epub 2013, Mar 6. PMID:23468426[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Daruzzaman A, Clifton IJ, Adlington RM, Baldwin JE, Rutledge PJ. The Interaction of Isopenicillin N Synthase with Homologated Substrate Analogues delta-(L-alpha-Aminoadipoyl)-L-homocysteinyl-D-Xaa Characterised by Protein Crystallography. Chembiochem. 2013 Mar 18;14(5):599-606. doi: 10.1002/cbic.201200728. Epub 2013, Mar 6. PMID:23468426 doi:http://dx.doi.org/10.1002/cbic.201200728
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