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6ow0
From Proteopedia
(Difference between revisions)
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| - | '''Unreleased structure''' | ||
| - | + | ==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]] 2.67Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[6ow0]] is a 2 chain structure. 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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6OW0 FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6ow0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ow0 OCA], [http://pdbe.org/6ow0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ow0 RCSB], [http://www.ebi.ac.uk/pdbsum/6ow0 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ow0 ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | <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®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 6ow0" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Hou, C]] | ||
| + | [[Category: Rohr, J]] | ||
| + | [[Category: Tsodikov, O V]] | ||
| + | [[Category: Yu, X]] | ||
| + | [[Category: Aureolic acid]] | ||
| + | [[Category: Biosynthesis]] | ||
| + | [[Category: Natural product]] | ||
| + | [[Category: Oxidoreductase]] | ||
| + | [[Category: Reductase]] | ||
Revision as of 06:51, 27 November 2019
Crystal structure of mithramycin 3-side chain keto-reductase MtmW in complex with NAD+ and PEG
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