6ovq: Difference between revisions
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==Crystal structure of mithramycin 3-side chain keto-reductase MtmW== | |||
<StructureSection load='6ovq' size='340' side='right'caption='[[6ovq]], [[Resolution|resolution]] 1.80Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6ovq]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6OVQ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6OVQ 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></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=6ovq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ovq OCA], [http://pdbe.org/6ovq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ovq RCSB], [http://www.ebi.ac.uk/pdbsum/6ovq PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ovq 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 6ovq" 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
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