9ha0

Crystal structure of Cu(II)-bound LmrR_V15Bpy variant BVS

spinqualitylabelsall models 9ha0, resolution 1.75Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 9ha0 is a 2 chain structure with sequence from Lactococcus lactis subsp. cremoris MG1363. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.75Å Ligands: BP5, CU, GOL, IMD Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function A2RI36_LACLM Publication Abstract from PubMed Artificial metalloenzymes (ArMs) are an attractive approach to achieving "new to nature" biocatalytic transformations. In this work, a novel copper-dependent artificial Michaelase (Cu_Michaelase) comprising a genetically encoded copper-binding ligand, i. e. (2,2-bipyridin-5-yl)alanine (BpyA), was developed. For the first time, such an ArM containing a non-canonical metal-binding amino acid was successfully optimized through directed evolution. The evolved Cu_Michaelase was applied in the copper-catalyzed asymmetric addition of 2-acetyl azaarenes to nitroalkenes, yielding various gamma-nitro butyric acid derivatives, which are precursors for a range of high-value-added pharmaceutically relevant compounds, with good yields and high enantioselectivities (up to >99 % yield and 99 % ee). Additionally, the evolved variant could be further used in a preparative-scale synthesis, providing chiral products for diverse derivatizations. X-ray crystal structure analysis confirmed the binding of Cu(II) ions to the BpyA residues and showed that, in principle, there is sufficient space for the 2-acetyl azaarene substrate to coordinate. Kinetic studies showed that the increased catalytic efficiency of the evolved enzyme is due to improvements in apparent K(M) for both substrates and a notable threefold increase in apparent k(cat) for 2-acetyl pyridine. This work illustrates the potential of artificial metalloenzymes exploiting non-canonical metal-binding ligands for new-to-nature biocatalysis. An Artificial Copper-Michaelase Featuring a Genetically Encoded Bipyridine Ligand for Asymmetric Additions to Nitroalkenes.,Jiang R, Casilli F, Thunnissen AWH, Roelfes G Angew Chem Int Ed Engl. 2025 Feb 13:e202423182. doi: 10.1002/anie.202423182. PMID:39945539 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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