View source for 5l40


==polyketide ketoreductase SimC7 - apo crystal form 1==
<StructureSection load='5l40' size='340' side='right'caption='[[5l40]], [[Resolution|resolution]] 1.60&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5l40]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Streptomyces_antibioticus Streptomyces antibioticus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5L40 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5L40 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]] 1.6&#8491;</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=5l40 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5l40 OCA], [https://pdbe.org/5l40 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5l40 RCSB], [https://www.ebi.ac.uk/pdbsum/5l40 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5l40 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/G9VYV4_STRAT G9VYV4_STRAT] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
SimC7 is a polyketide ketoreductase involved in biosynthesis of the angucyclinone moiety of the gyrase inhibitor simocyclinone D8 (SD8). SimC7, which belongs to the short-chain dehydrogenase/reductase (SDR) superfamily, catalyzes reduction of the C-7 carbonyl of the angucyclinone, and the resulting hydroxyl is essential for antibiotic activity. SimC7 shares little sequence similarity with characterized ketoreductases, suggesting it might have a distinct mechanism. To investigate this possibility, we determined the structures of SimC7 alone, with NADP(+), and with NADP(+) and the substrate 7-oxo-SD8. These structures show that SimC7 is distinct from previously characterized polyketide ketoreductases, lacking the conserved catalytic triad, including the active-site tyrosine that acts as central acid-base catalyst in canonical SDR proteins. Taken together with functional analyses of active-site mutants, our data suggest that SimC7 catalyzes a substrate-assisted, two-step reaction for reduction of the C-7 carbonyl group involving intramolecular transfer of a substrate-derived proton to generate a phenolate intermediate.

Substrate-Assisted Catalysis in Polyketide Reduction Proceeds via a Phenolate Intermediate.,Schafer M, Stevenson CE, Wilkinson B, Lawson DM, Buttner MJ Cell Chem Biol. 2016 Sep 22;23(9):1091-7. doi: 10.1016/j.chembiol.2016.07.018., Epub 2016 Sep 8. PMID:27617849<ref>PMID:27617849</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5l40" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Streptomyces antibioticus]]
[[Category: Buttner MJ]]
[[Category: Lawson DM]]
[[Category: Schafer M]]
[[Category: Stevenson CEM]]
[[Category: Wilkinson B]]