View source for 6ow0


==Crystal structure of mithramycin 3-side chain keto-reductase MtmW in complex with NAD+ and PEG==
<StructureSection load='6ow0' size='340' side='right'caption='[[6ow0]], [[Resolution|resolution]] 2.67&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6ow0]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Streptomyces_argillaceus Streptomyces argillaceus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6OW0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6OW0 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]] 2.67&#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=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</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=6ow0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ow0 OCA], [https://pdbe.org/6ow0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6ow0 RCSB], [https://www.ebi.ac.uk/pdbsum/6ow0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6ow0 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/Q194Q1_STRAA Q194Q1_STRAA] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
MtmOIV and MtmW catalyze the final two reactions in the mithramycin (MTM) biosynthetic pathway, the Baeyer-Villiger opening of the fourth ring of premithramycin B (PMB), creating the C3 pentyl side chain, strictly followed by reduction of the distal keto group on the new side chain. Unexpectedly this results in a C2 stereoisomer of mithramycin, iso-mithramycin (iso-MTM). Iso-MTM undergoes a non-enzymatic isomerization to MTM catalyzed by Mg2+ ions. Crystal structures of MtmW and its complexes with co-substrate NADPH and PEG, suggest a catalytic mechanism of MtmW. The structures also show that a tetrameric assembly of this enzyme strikingly resembles of the ring-shaped beta subunit of a vertebrate ion channel. We show that MtmW and MmOIV form a complex in the presence of PMB and NADPH, presumably to hand over the unstable MtmOIV product to MtmW, yielding iso-MTM, as a potential self-resistance mechanism against MTM toxicity.

Discovery of a Cryptic Intermediate in Late Steps of Mithramycin Biosynthesis.,Wheeler R, Yu X, Hou C, Mitra P, Chen JM, Herkules F, Ivanov DN, Tsodikov OV, Rohr J Angew Chem Int Ed Engl. 2019 Nov 8. doi: 10.1002/anie.201910241. PMID:31702856<ref>PMID:31702856</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6ow0" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Streptomyces argillaceus]]
[[Category: Hou C]]
[[Category: Rohr J]]
[[Category: Tsodikov OV]]
[[Category: Yu X]]