View source for 5epa


==Crystal structure of non-heme alpha ketoglutarate dependent carbocyclase SnoK from nogalamycin biosynthesis==
<StructureSection load='5epa' size='340' side='right'caption='[[5epa]], [[Resolution|resolution]] 2.24&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5epa]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Streptomyces_nogalater Streptomyces nogalater]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5EPA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5EPA 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]] 2.24&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AKG:2-OXOGLUTARIC+ACID'>AKG</scene>, <scene name='pdbligand=FE:FE+(III)+ION'>FE</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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=5epa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5epa OCA], [https://pdbe.org/5epa PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5epa RCSB], [https://www.ebi.ac.uk/pdbsum/5epa PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5epa ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/Q9RN60_STRNO Q9RN60_STRNO] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Nogalamycin, an aromatic polyketide displaying high cytotoxicity, has a unique structure, with one of the carbohydrate units covalently attached to the aglycone via an additional carbon-carbon bond. The underlying chemistry, which implies a particularly challenging reaction requiring activation of an aliphatic carbon atom, has remained enigmatic. Here, we show that the unusual C5''-C2 carbocyclization is catalyzed by the non-heme iron alpha-ketoglutarate (alpha-KG)-dependent SnoK in the biosynthesis of the anthracycline nogalamycin. The data are consistent with a mechanistic proposal whereby the Fe(IV) = O center abstracts the H5'' atom from the amino sugar of the substrate, with subsequent attack of the aromatic C2 carbon on the radical center. We further show that, in the same metabolic pathway, the homologous SnoN (38% sequence identity) catalyzes an epimerization step at the adjacent C4'' carbon, most likely via a radical mechanism involving the Fe(IV) = O center. SnoK and SnoN have surprisingly similar active site architectures considering the markedly different chemistries catalyzed by the enzymes. Structural studies reveal that the differences are achieved by minor changes in the alignment of the substrates in front of the reactive ferryl-oxo species. Our findings significantly expand the repertoire of reactions reported for this important protein family and provide an illustrative example of enzyme evolution.

Divergent non-heme iron enzymes in the nogalamycin biosynthetic pathway.,Siitonen V, Selvaraj B, Niiranen L, Lindqvist Y, Schneider G, Metsa-Ketela M Proc Natl Acad Sci U S A. 2016 May 10;113(19):5251-6. doi:, 10.1073/pnas.1525034113. Epub 2016 Apr 25. PMID:27114534<ref>PMID:27114534</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5epa" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Streptomyces nogalater]]
[[Category: Lindqvist Y]]
[[Category: Metsa-Ketela M]]
[[Category: Niiranen L]]
[[Category: Schneider G]]
[[Category: Selvaraj B]]
[[Category: Siitonen V]]