View source for 9otb


==Crystal structure of SwnH2==
<StructureSection load='9otb' size='340' side='right'caption='[[9otb]], [[Resolution|resolution]] 2.28&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9otb]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Metarhizium_robertsii Metarhizium robertsii]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9OTB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9OTB 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]] 2.28&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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=9otb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9otb OCA], [https://pdbe.org/9otb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9otb RCSB], [https://www.ebi.ac.uk/pdbsum/9otb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9otb ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/SWNH2_METRA SWNH2_METRA] Dioxygenase; part of the gene cluster that mediates the biosynthesis of swainsonine (SW), a cytotoxic fungal alkaloid and a potential cancer therapy drug (PubMed:28381497, PubMed:32786262). Swainsonine production occurs via a multibranched pathway and is dispensable for fungal colonization of plants and infection of insect hosts (PubMed:32786262). The first step of swainsonine biosynthesis is the production of the precursor pipecolic acid (PA) via conversion of L-lysine (Lys) to 1-piperideine-6-carboxylate (P6C) by the aminotransferase swnA, the latter being further reduced to PA by the reductase swnR (PubMed:32786262). PA can be converted from lysine by both the SW biosynthetic cluster and the unclustered genes such as lysine cyclodeaminase (PubMed:32786262). The PKS-NRPS hybrid synthetase swnK uptakes and condensates PA and malonyl-CoA with and without skipping of the ketoreductase (KR) domain in order to produce 3 intermediates, 1-oxoindolizidine, (1S)-1-hydroxyindolizin, and (1R)-1-hydroxyindolizine; with the transisomer (1S)-1-hydroxyindolizin being predominant (PubMed:32786262). The terminal thioester reductase (TE) domain of swnK is involved in reduction of the thioester bond to release the intermediate aldehydes (PubMed:32786262). The oxidoreductase swnN could contribute to the reduction of 1-oxoindolizidine to (1S)-1-hydroxyindolizin and (1R)-1-hydroxyindolizine, contributing to the major route of SW production (Probable). The dioxygenase swnH2 would be responsible for the oxidization of (1R)-1-hydroxyindolizine into (1R,2S)-1,2-dihydroxyindolizine and of (1S)-1-hydroxyindolizin to yield both (1R,2S)-1,2-dihydroxyindolizine and (1S,2S)-1,2-dihydroxyindolizine (PubMed:32786262). The dioxygenase swnH1 then performs the conversion of the 1,2-dihydroxyindolizine epimers to SW (PubMed:32786262).<ref>PMID:28381497</ref> <ref>PMID:32786262</ref> <ref>PMID:32786262</ref> 
== References ==
<references/>
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</StructureSection>
[[Category: Large Structures]]
[[Category: Metarhizium robertsii]]
[[Category: Hai Y]]
[[Category: Xi W]]