7xee

From Proteopedia

Crystal Structure of the Y53F/N55A mutant of LEH complexed with 2-(3-phenyloxetan-3-yl)ethanamine

Structural highlights

7xee is a 2 chain structure with sequence from Rhodococcus erythropolis. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.877Å
Ligands:	, ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

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.

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^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Li JK, Qu G, Li X, Tian Y, Cui C, Zhang FG, Zhang W, Ma JA, Reetz MT, Sun Z. Rational enzyme design for enabling biocatalytic Baldwin cyclization and asymmetric synthesis of chiral heterocycles. Nat Commun. 2022 Dec 19;13(1):7813. doi: 10.1038/s41467-022-35468-y. PMID:36535947 doi:http://dx.doi.org/10.1038/s41467-022-35468-y