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| <StructureSection load='5tz6' size='340' side='right'caption='[[5tz6]], [[Resolution|resolution]] 2.40Å' scene=''> | | <StructureSection load='5tz6' size='340' side='right'caption='[[5tz6]], [[Resolution|resolution]] 2.40Å' scene=''> |
| == Structural highlights == | | == Structural highlights == |
- | <table><tr><td colspan='2'>[[5tz6]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Lyngbya_majuscula_3l Lyngbya majuscula 3l]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5TZ6 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5TZ6 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5tz6]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Moorena_producens_3L Moorena producens 3L]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5TZ6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5TZ6 FirstGlance]. <br> |
- | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=7OD:(2E,5R)-5-HYDROXY-2-METHYLHEPT-2-ENOIC+ACID'>7OD</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]] 2.4Å</td></tr> |
- | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5tz5|5tz5]], [[5tz7|5tz7]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=7OD:(2E,5R)-5-HYDROXY-2-METHYLHEPT-2-ENOIC+ACID'>7OD</scene></td></tr> |
- | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">LYNGBM3L_74460 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=489825 Lyngbya majuscula 3L])</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=5tz6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5tz6 OCA], [https://pdbe.org/5tz6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5tz6 RCSB], [https://www.ebi.ac.uk/pdbsum/5tz6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5tz6 ProSAT]</span></td></tr> |
- | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5tz6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5tz6 OCA], [http://pdbe.org/5tz6 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5tz6 RCSB], [http://www.ebi.ac.uk/pdbsum/5tz6 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5tz6 ProSAT]</span></td></tr> | + | |
| </table> | | </table> |
| + | == Function == |
| + | [https://www.uniprot.org/uniprot/F4Y426_9CYAN F4Y426_9CYAN] |
| <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| </StructureSection> | | </StructureSection> |
| [[Category: Large Structures]] | | [[Category: Large Structures]] |
- | [[Category: Lyngbya majuscula 3l]] | + | [[Category: Moorena producens 3L]] |
- | [[Category: Dodge, G J]] | + | [[Category: Dodge GJ]] |
- | [[Category: Smith, J L]] | + | [[Category: Smith JL]] |
- | [[Category: Curacin]]
| + | |
- | [[Category: Dehydratase]]
| + | |
- | [[Category: Lyase-lyase inhibitor complex]]
| + | |
- | [[Category: Polyketide synthase]]
| + | |
| Structural highlights
Function
F4Y426_9CYAN
Publication Abstract from PubMed
Polyketide synthase (PKS) enzymes continue to hold great promise as synthetic biology platforms for the production of novel therapeutic agents, biofuels, and commodity chemicals. Dehydratase (DH) catalytic domains play an important role during polyketide biosynthesis through the dehydration of the nascent polyketide intermediate to provide olefins. Our understanding of the detailed mechanistic and structural underpinning of DH domains that control substrate specificity and selectivity remains limited, thus hindering our efforts to rationally re-engineer PKSs. The curacin pathway houses a rare plurality of possible double bond permutations containing conjugated olefins as well as both cis- and trans-olefins, providing an unrivaled model system for polyketide dehydration. All four DH domains implicated in curacin biosynthesis were characterized in vitro using synthetic substrates, and activity was measured by LC-MS/MS analysis. These studies resulted in complete kinetic characterization of the all-trans-trienoate-forming CurK-DH, whose kcat of 72 s-1 is more than 3 orders of magnitude greater than that of any previously reported PKS DH domain. A novel stereospecific mechanism for diene formation involving a vinylogous enolate intermediate is proposed for the CurJ and CurH DHs on the basis of incubation studies with truncated substrates. A synthetic substrate was co-crystallized with a catalytically inactive Phe substitution in the His-Asp catalytic dyad of CurJ-DH to elucidate substrate-enzyme interactions. The resulting complex suggested the structural basis for dienoate formation and provided the first glimpse into the enzyme-substrate interactions essential for the formation of olefins in polyketide natural products. This examination of both canonical and non-canonical dehydration mechanisms reveals hidden catalytic activity inherent in some DH domains that may be leveraged for future applications in synthetic biology.
Vinylogous Dehydration by a Polyketide Dehydratase Domain in Curacin Biosynthesis.,Fiers WD, Dodge GJ, Sherman DH, Smith JL, Aldrich CC J Am Chem Soc. 2016 Dec 14;138(49):16024-16036. Epub 2016 Nov 30. PMID:27960309[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Fiers WD, Dodge GJ, Sherman DH, Smith JL, Aldrich CC. Vinylogous Dehydration by a Polyketide Dehydratase Domain in Curacin Biosynthesis. J Am Chem Soc. 2016 Dec 14;138(49):16024-16036. Epub 2016 Nov 30. PMID:27960309 doi:http://dx.doi.org/10.1021/jacs.6b09748
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