View source for 8hwy


==Ancestral imine reductase mutant N559_M6==
<StructureSection load='8hwy' size='340' side='right'caption='[[8hwy]], [[Resolution|resolution]] 2.32&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8hwy]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia Escherichia]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8HWY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8HWY 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]] 2.32&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</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=8hwy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8hwy OCA], [https://pdbe.org/8hwy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8hwy RCSB], [https://www.ebi.ac.uk/pdbsum/8hwy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8hwy ProSAT]</span></td></tr>
</table>
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== Publication Abstract from PubMed ==
The stereoselectivity of enzymes plays a central role in asymmetric biocatalytic reactions, but there remains a dearth of evolution-driven biochemistry studies investigating the evolutionary trajectory of this vital property. Imine reductases (IREDs) are one such enzyme that possesses excellent stereoselectivity, and stereocomplementary members are pervasive in the family. However, the regulatory mechanism behind stereocomplementarity remains cryptic. Herein, we reconstruct a panel of active ancestral IREDs and trace the evolution of stereoselectivity from ancestors to extant IREDs. Combined with coevolution analysis, we reveal six historical mutations capable of recapitulating stereoselectivity evolution. An investigation of the mechanism with X-ray crystallography shows that they collectively reshape the substrate-binding pocket to regulate stereoselectivity inversion. In addition, we construct an empirical fitness landscape and discover that epistasis is prevalent in stereoselectivity evolution. Our findings emphasize the power of ASR in circumventing the time-consuming large-scale mutagenesis library screening for identifying mutations that change functions and support a Darwinian premise from a molecular perspective that the evolution of biological functions is a stepwise process.

Evolutionary insights into the stereoselectivity of imine reductases based on ancestral sequence reconstruction.,Zhu XX, Zheng WQ, Xia ZW, Chen XR, Jin T, Ding XW, Chen FF, Chen Q, Xu JH, Kong XD, Zheng GW Nat Commun. 2024 Nov 28;15(1):10330. doi: 10.1038/s41467-024-54613-3. PMID:39609402<ref>PMID:39609402</ref>

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