4ufn

Laboratory evolved variant R-C1B1 of potato epoxide hydrolase StEH1

spinqualitylabelsall models 4ufn, resolution 2.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4ufn is a 2 chain structure with sequence from Solanum tuberosum. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2Å Ligands: DIO Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function Q41415_SOLTU Publication Abstract from PubMed Potato epoxide hydrolase 1 (StEH1) is a biocatalytically important enzyme that exhibits rich enantio- and regioselectivity in the hydrolysis of chiral epoxide substrates. In particular, StEH1 has been demonstrated to enantioconvergently hydrolyze racemic mixes of styrene oxide (SO) to yield (R)-1-phenylethanediol. This work combines computational, crystallographic and biochemical analyses to understand both the origins of the enantioconvergent behavior of the wild-type enzyme, as well as shifts in activities and substrate binding preferences in an engineered StEH1 variant, R-C1B1, which contains four active site substitutions (W106L, L109Y, V141K and I155V). Our calculations are able to reproduce both the enantio- and regioselectivities of StEH1, and demonstrate a clear link between different substrate binding modes and the corresponding selectivity, with the preferred binding modes being shifted between the wild-type enzyme and the R-C1B1 variant. Additionally, we demonstrate that the observed changes in selectivity and the corresponding enantioconvergent behavior are due to a combination of steric and electrostatic effects that modulate both the accessibility of the different carbon atoms to the nucleophilic side chain of D105, as well as the interactions between the substrate and protein amino acid side chains and active site water molecules. Being able to computationally predict such subtle effects for different substrate enantiomers, as well as to understand their origin and how they are affected by mutations, is an important advance towards the computational design of improved biocatalysts for enantioselective synthesis. Conformational diversity and enantioconvergence in potato epoxide hydrolase 1.,Bauer P, Carlsson AJ, Amrein BA, Dobritzsch D, Widersten M, Kamerlin SC Org Biomol Chem. 2016 Jun 28;14(24):5639-51. doi: 10.1039/c6ob00060f. Epub 2016, Apr 6. PMID:27049844 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Epoxide hydrolase 3D structures

Proteopedia Page Contributors and Editors (what is this?)

OCA