View source for 6ypz


==Promiscuous Reductase LugOII Catalyzes Keto-reduction at C1 during Lugdunomycin Biosynthesis==
<StructureSection load='6ypz' size='340' side='right'caption='[[6ypz]], [[Resolution|resolution]] 1.08&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6ypz]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Streptomyces_sp._QL37 Streptomyces sp. QL37]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6YPZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6YPZ 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]] 1.08&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</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=6ypz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ypz OCA], [https://pdbe.org/6ypz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6ypz RCSB], [https://www.ebi.ac.uk/pdbsum/6ypz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6ypz ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/A0A2S6PN47_9ACTN A0A2S6PN47_9ACTN] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Angucyclines are a structurally diverse class of actinobacterial natural products defined by their varied polycyclic ring systems, which display a wide range of biological activities. We recently discovered lugdunomycin (1), a highly rearranged polyketide antibiotic derived from the angucycline backbone that is synthesized via several yet unexplained enzymatic reactions. Here, we show via in vivo, in vitro, and structural analysis that the promiscuous reductase LugOII catalyzes both a C6 and an unprecedented C1 ketoreduction. This then sets the stage for the subsequent C-ring cleavage that is key to the rearranged scaffolds of 1. The 1.1 A structures of LugOII in complex with either ligand 8-O-Methylrabelomycin (4) or 8-O-Methyltetrangomycin (5) and of apoenzyme were resolved, which revealed a canonical Rossman fold and a remarkable conformational change during substrate capture and release. Mutational analysis uncovered key residues for substrate access, position, and catalysis as well as specific determinants that control its dual functionality. The insights obtained in this work hold promise for the discovery and engineering of other promiscuous reductases that may be harnessed for the generation of novel biocatalysts for chemoenzymatic applications.

Functional and Structural Insights into a Novel Promiscuous Ketoreductase of the Lugdunomycin Biosynthetic Pathway.,Xiao X, Elsayed SS, Wu C, van der Heul HU, Metsa-Ketela M, Du C, Prota AE, Chen CC, Liu W, Guo RT, Abrahams JP, van Wezel GP ACS Chem Biol. 2020 Sep 8. doi: 10.1021/acschembio.0c00564. PMID:32840360<ref>PMID:32840360</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6ypz" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Streptomyces sp. QL37]]
[[Category: Abrahams JP]]
[[Category: Elsayed SS]]
[[Category: Guo R]]
[[Category: Huang J]]
[[Category: Prota A]]
[[Category: Wu C]]
[[Category: Xiao X]]
[[Category: Van Wezel GP]]
[[Category: Van der Heul H]]