View source for 5inf


==Structural basis for acyl-CoA carboxylase-mediated assembly of unusual polyketide synthase extender units incorporated into the stambomycin antibiotics==
<StructureSection load='5inf' size='340' side='right'caption='[[5inf]], [[Resolution|resolution]] 2.75&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5inf]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Streptomyces_ambofaciens_ATCC_23877 Streptomyces ambofaciens ATCC 23877]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5INF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5INF 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]] 2.751&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=HXC:HEXANOYL-COENZYME+A'>HXC</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=5inf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5inf OCA], [https://pdbe.org/5inf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5inf RCSB], [https://www.ebi.ac.uk/pdbsum/5inf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5inf ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/A0ACI9_STRA7 A0ACI9_STRA7] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Type 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<ref>PMID:28000660</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5inf" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Streptomyces ambofaciens ATCC 23877]]
[[Category: Challis GL]]
[[Category: Miyazawa T]]
[[Category: Osada H]]
[[Category: Ray L]]
[[Category: Song L]]
[[Category: Tsai SC]]
[[Category: Valentic TR]]
[[Category: Withall DM]]