View source for 6kog


==Ketosynthase domain in tenuazonic acid synthetase 1 (TAS1).==
<StructureSection load='6kog' size='340' side='right'caption='[[6kog]], [[Resolution|resolution]] 1.68&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6kog]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Pyricularia_oryzae_70-15 Pyricularia oryzae 70-15]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6KOG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6KOG 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]] 1.68&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</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'>[https://proteopedia.org/fgij/fg.htm?mol=6kog FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6kog OCA], [https://pdbe.org/6kog PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6kog RCSB], [https://www.ebi.ac.uk/pdbsum/6kog PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6kog ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/TAS1_MAGO7 TAS1_MAGO7] Hybrid PKS-NRPS synthetase that mediates the biosynthesis of the toxin tenuazonic acid (TeA), an inhibitor of protein biosynthesis on ribosomes by suppressing the release of new protein (PubMed:26503170). TAS1 alone is sufficient for TeA synthesis (PubMed:26503170). The NRPS part performs the condensation of isoleucine with acetoacetyl-CoA and the final cyclization step is conducted by the KS domain (PubMed:26503170).<ref>PMID:26503170</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Many microbial secondary metabolites are produced by multienzyme complexes comprising non-ribosomal peptide synthetases (NRPSs) and polyketide synthases (PKSs). The ketosynthase (KS) domains of polyketide synthase normally catalyze the decarboxylative Claisen condensation of acyl and malonyl blocks to extend the polyketide chain. However, the terminal KS domain in tenuazonic acid synthetase 1 (TAS1) from the fungus Pyricularia oryzae conducts substrate cyclization. Here, we report on the unique features of the KS domain in TAS1. We observed that this domain is monomeric, not dimeric as is typical for KSs. Analysis of a 1.68 A-resolution crystal structure suggests that the substrate cyclization is triggered via proton abstraction from the active methylene moiety in the substrate by a catalytic His-322 residue. Additionally, we show that TAS1 KS promiscuously accepts amino acyl substrates and that this promiscuity can be increased by a single amino acid substitution in the substrate-binding pocket of the enzyme. These findings provide insight into a KS domain that accepts the amino acid-containing substrate in an NRPS-PKS hybrid enzyme and provide hints to the substrate cyclization mechanism performed by the KS domain in the biosynthesis of the mycotoxin tenuazonic acid.

Unique features of the ketosynthase domain in a non-ribosomal peptide synthetase-polyketide synthase hybrid enzyme, tenuazonic acid synthetase 1.,Yun CS, Nishimoto K, Motoyama T, Shimizu T, Hino T, Dohmae N, Nagano S, Osada H J Biol Chem. 2020 Jun 21. pii: RA120.013105. doi: 10.1074/jbc.RA120.013105. PMID:32565425<ref>PMID:32565425</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6kog" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Pyricularia oryzae 70-15]]
[[Category: Hino T]]
[[Category: Motoyama T]]
[[Category: Nagano S]]
[[Category: Nishimoto K]]
[[Category: Osada H]]
[[Category: Yun CS]]