7vx2: Difference between revisions
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==Crystal Structure of the Y53F/N55A/I80F/L114V/I116V mutant of LEH== | |||
<StructureSection load='7vx2' size='340' side='right'caption='[[7vx2]], [[Resolution|resolution]] 2.48Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[7vx2]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Rhodococcus_erythropolis Rhodococcus erythropolis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7VX2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7VX2 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]] 2.485Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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'>[https://proteopedia.org/fgij/fg.htm?mol=7vx2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7vx2 OCA], [https://pdbe.org/7vx2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7vx2 RCSB], [https://www.ebi.ac.uk/pdbsum/7vx2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7vx2 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/LIMA_RHOER LIMA_RHOER] Catalyzes the conversion of limonene-1,2-epoxide to limonene-1,2-diol. Can use both the (-) and (+) isomers of limonene-1,2-epoxide as substrates and also has some activity with 1-methylcyclohexene oxide, cyclohexene oxide and indene oxide as substrates. | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Chiral heterocyclic compounds are needed for important medicinal applications. We report an in silico strategy for the biocatalytic synthesis of chiral N- and O-heterocycles via Baldwin cyclization modes of hydroxy- and amino-substituted epoxides and oxetanes using the limonene epoxide hydrolase from Rhodococcus erythropolis. This enzyme normally catalyzes hydrolysis with formation of vicinal diols. Firstly, the required shutdown of the undesired natural water-mediated ring-opening is achieved by rational mutagenesis of the active site. In silico enzyme design is then continued with generation of the improved mutants. These variants prove to be versatile catalysts for preparing chiral N- and O-heterocycles with up to 99% conversion, and enantiomeric ratios up to 99:1. Crystal structural data and computational modeling reveal that Baldwin-type cyclizations, catalyzed by the reprogrammed enzyme, are enabled by reshaping the active-site environment that directs the distal RHN and HO-substituents to be intramolecular nucleophiles. | |||
Rational enzyme design for enabling biocatalytic Baldwin cyclization and asymmetric synthesis of chiral heterocycles.,Li JK, Qu G, Li X, Tian Y, Cui C, Zhang FG, Zhang W, Ma JA, Reetz MT, Sun Z Nat Commun. 2022 Dec 19;13(1):7813. doi: 10.1038/s41467-022-35468-y. PMID:36535947<ref>PMID:36535947</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 7vx2" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Epoxide hydrolase 3D structures|Epoxide hydrolase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Rhodococcus erythropolis]] | |||
[[Category: Han X]] | |||
[[Category: Li X]] | |||
[[Category: Liu WD]] | |||
[[Category: Qu G]] | |||
[[Category: Sun ZT]] | |||
Latest revision as of 20:33, 29 November 2023
Crystal Structure of the Y53F/N55A/I80F/L114V/I116V mutant of LEHCrystal Structure of the Y53F/N55A/I80F/L114V/I116V mutant of LEH
Structural highlights
FunctionLIMA_RHOER Catalyzes the conversion of limonene-1,2-epoxide to limonene-1,2-diol. Can use both the (-) and (+) isomers of limonene-1,2-epoxide as substrates and also has some activity with 1-methylcyclohexene oxide, cyclohexene oxide and indene oxide as substrates. Publication Abstract from PubMedChiral heterocyclic compounds are needed for important medicinal applications. We report an in silico strategy for the biocatalytic synthesis of chiral N- and O-heterocycles via Baldwin cyclization modes of hydroxy- and amino-substituted epoxides and oxetanes using the limonene epoxide hydrolase from Rhodococcus erythropolis. This enzyme normally catalyzes hydrolysis with formation of vicinal diols. Firstly, the required shutdown of the undesired natural water-mediated ring-opening is achieved by rational mutagenesis of the active site. In silico enzyme design is then continued with generation of the improved mutants. These variants prove to be versatile catalysts for preparing chiral N- and O-heterocycles with up to 99% conversion, and enantiomeric ratios up to 99:1. Crystal structural data and computational modeling reveal that Baldwin-type cyclizations, catalyzed by the reprogrammed enzyme, are enabled by reshaping the active-site environment that directs the distal RHN and HO-substituents to be intramolecular nucleophiles. Rational enzyme design for enabling biocatalytic Baldwin cyclization and asymmetric synthesis of chiral heterocycles.,Li JK, Qu G, Li X, Tian Y, Cui C, Zhang FG, Zhang W, Ma JA, Reetz MT, Sun Z Nat Commun. 2022 Dec 19;13(1):7813. doi: 10.1038/s41467-022-35468-y. PMID:36535947[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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