View source for 8qhe


==Crystal structure IR-09==
<StructureSection load='8qhe' size='340' side='right'caption='[[8qhe]], [[Resolution|resolution]] 1.60&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8qhe]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Aspergillus_lentulus Aspergillus lentulus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8QHE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8QHE 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]] 1.6&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</scene>, <scene name='pdbligand=VCU:~{N}-methylcyclohexanamine'>VCU</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=8qhe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8qhe OCA], [https://pdbe.org/8qhe PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8qhe RCSB], [https://www.ebi.ac.uk/pdbsum/8qhe PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8qhe ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/A0A0S7DXU4_9EURO A0A0S7DXU4_9EURO] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Novel building blocks are in constant demand during the search for innovative bioactive small molecule therapeutics by enabling the construction of structure-activity-property-toxicology relationships. Complex chiral molecules containing multiple stereocenters are an important component in compound library expansion but can be difficult to access by traditional organic synthesis. Herein, we report a biocatalytic process to access a specific diastereomer of a chiral amine building block used in drug discovery. A reductive aminase (RedAm) was engineered following a structure-guided mutagenesis strategy to produce the desired isomer. The engineered RedAm (IR-09 W204R) was able to generate the (S,S,S)-isomer 3 in 45% conversion and 95% ee from the racemic ketone 2. Subsequent palladium-catalyzed deallylation of 3 yielded the target primary amine 4 in a 73% yield. This engineered biocatalyst was used at preparative scale and represents a potential starting point for further engineering and process development.

Biocatalysis in Drug Design: Engineered Reductive Aminases (RedAms) Are Used to Access Chiral Building Blocks with Multiple Stereocenters.,Casamajo AR, Yu Y, Schnepel C, Morrill C, Barker R, Levy CW, Finnigan J, Spelling V, Westerlund K, Petchey M, Sheppard RJ, Lewis RJ, Falcioni F, Hayes MA, Turner NJ J Am Chem Soc. 2023 Oct 2. doi: 10.1021/jacs.3c07010. PMID:37782882<ref>PMID:37782882</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8qhe" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Aspergillus lentulus]]
[[Category: Large Structures]]
[[Category: Levy CW]]