View source for 8u04


==Reductasporine biosynthetic pathway imine reductase RedE, apo==
<StructureSection load='8u04' size='340' side='right'caption='[[8u04]], [[Resolution|resolution]] 1.62&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8u04]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Uncultured_bacterium Uncultured bacterium]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8U04 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8U04 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]] 1.62&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=CME:S,S-(2-HYDROXYETHYL)THIOCYSTEINE'>CME</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=IOD:IODIDE+ION'>IOD</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=8u04 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8u04 OCA], [https://pdbe.org/8u04 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8u04 RCSB], [https://www.ebi.ac.uk/pdbsum/8u04 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8u04 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/A0A0F7G0Y4_9BACT A0A0F7G0Y4_9BACT] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Imine reductases (IREDs) and reductive aminases have been used in the synthesis of chiral amine products for drug manufacturing; however, little is known about their biological contexts. Here we employ structural studies and site-directed mutagenesis to interrogate the mechanism of the IRED RedE from the biosynthetic pathway to the indolocarbazole natural product reductasporine. Cocrystal structures with the substrate-mimic arcyriaflavin A reveal an extended active site cleft capable of binding two indolocarbazole molecules. Site-directed mutagenesis of a conserved aspartate in the primary binding site reveals a new role for this residue in anchoring the substrate above the NADPH cofactor. Variants targeting the secondary binding site greatly reduce catalytic efficiency, while accumulating oxidized side-products. As indolocarbazole biosynthetic intermediates are susceptible to spontaneous oxidation, we propose the secondary site acts to protect against autooxidation, and the primary site drives catalysis through precise substrate orientation and desolvation effects. The structure of RedE with its extended active site can be the starting point as a new scaffold for engineering IREDs and reductive aminases to intercept large substrates relevant to industrial applications.

An imine reductase that captures reactive intermediates in the biosynthesis of the indolocarbazole reductasporine.,Daniel-Ivad P, Ryan KS J Biol Chem. 2024 Feb;300(2):105642. doi: 10.1016/j.jbc.2024.105642. Epub 2024 , Jan 8. PMID:38199566<ref>PMID:38199566</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8u04" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Uncultured bacterium]]
[[Category: Daniel-Ivad P]]
[[Category: Ryan KS]]