5ing: Difference between revisions
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==A crotonyl-CoA reductase-carboxylase independent pathway for assembly of unusual alkylmalonyl-CoA polyketide synthase extender unit== | ==A crotonyl-CoA reductase-carboxylase independent pathway for assembly of unusual alkylmalonyl-CoA polyketide synthase extender unit== | ||
<StructureSection load='5ing' size='340' side='right' caption='[[5ing]], [[Resolution|resolution]] 2.45Å' scene=''> | <StructureSection load='5ing' size='340' side='right'caption='[[5ing]], [[Resolution|resolution]] 2.45Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[5ing]] is a 6 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5ING OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5ING FirstGlance]. <br> | <table><tr><td colspan='2'>[[5ing]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Stra7 Stra7]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5ING OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5ING FirstGlance]. <br> | ||
</td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr> | </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5ini|5ini]], [[5inf|5inf]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5ini|5ini]], [[5inf|5inf]]</td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">SAM23877_7108, SAMR0483 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=278992 STRA7])</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=5ing FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ing OCA], [http://pdbe.org/5ing PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ing RCSB], [http://www.ebi.ac.uk/pdbsum/5ing PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5ing ProSAT]</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=5ing FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ing OCA], [http://pdbe.org/5ing PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ing RCSB], [http://www.ebi.ac.uk/pdbsum/5ing PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5ing ProSAT]</span></td></tr> | ||
</table> | </table> | ||
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__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | |||
[[Category: Stra7]] | |||
[[Category: Challis, G L]] | [[Category: Challis, G L]] | ||
[[Category: Milligan, J C]] | [[Category: Milligan, J C]] | ||
Revision as of 14:50, 25 December 2019
A crotonyl-CoA reductase-carboxylase independent pathway for assembly of unusual alkylmalonyl-CoA polyketide synthase extender unitA crotonyl-CoA reductase-carboxylase independent pathway for assembly of unusual alkylmalonyl-CoA polyketide synthase extender unit
Structural highlights
Publication Abstract from PubMedType I modular polyketide synthases assemble diverse bioactive natural products. Such multienzymes typically use malonyl and methylmalonyl-CoA building blocks for polyketide chain assembly. However, in several cases more exotic alkylmalonyl-CoA extender units are also known to be incorporated. In all examples studied to date, such unusual extender units are biosynthesized via reductive carboxylation of alpha, beta-unsaturated thioesters catalysed by crotonyl-CoA reductase/carboxylase (CCRC) homologues. Here we show using a chemically-synthesized deuterium-labelled mechanistic probe, and heterologous gene expression experiments that the unusual alkylmalonyl-CoA extender units incorporated into the stambomycin family of polyketide antibiotics are assembled by direct carboxylation of medium chain acyl-CoA thioesters. X-ray crystal structures of the unusual beta-subunit of the acyl-CoA carboxylase (YCC) responsible for this reaction, alone and in complex with hexanoyl-CoA, reveal the molecular basis for substrate recognition, inspiring the development of methodology for polyketide bio-orthogonal tagging via incorporation of 6-azidohexanoic acid and 8-nonynoic acid into novel stambomycin analogues. A crotonyl-CoA reductase-carboxylase independent pathway for assembly of unusual alkylmalonyl-CoA polyketide synthase extender units.,Ray L, Valentic TR, Miyazawa T, Withall DM, Song L, Milligan JC, Osada H, Takahashi S, Tsai SC, Challis GL Nat Commun. 2016 Dec 21;7:13609. doi: 10.1038/ncomms13609. PMID:28000660[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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