9ful | pdb_00009ful

Crystal structure of SNAr1.3 in complex with iodide

spinqualitylabelsall models 9ful, resolution 1.88Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 9ful is a 1 chain structure with sequence from Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.88Å Ligands: IOD, PG4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Nucleophilic aromatic substitutions (S(N)Ar) are amongst the most widely used processes in the pharmaceutical and agrochemical industries(1-4), allowing convergent assembly of complex molecules through C-C and C-X (X = O, N, S) bond formation. S(N)Ar reactions are typically carried out using forcing conditions, involving polar aprotic solvents, stoichiometric bases and elevated temperatures, which do not allow for control over reaction selectivity. Despite the importance of S(N)Ar chemistry, there are only a handful of selective catalytic methods reported that rely on small organic hydrogen-bonding or phase-transfer catalysts(5-11). Here we establish a biocatalytic approach to stereoselective S(N)Ar chemistry by uncovering promiscuous S(N)Ar activity in a designed enzyme featuring an activated arginine(12). This activity was optimized over successive rounds of directed evolution to afford an engineered biocatalyst, S(N)Ar1.3, that is 160-fold more efficient than the parent and promotes the coupling of electron-deficient arenes with carbon nucleophiles with near-perfect stereocontrol (>99% e.e.). S(N)Ar1.3 can operate at a rate of 0.15 s(-1), perform >4000 turnovers and can accept a broad range of electrophilic and nucleophilic coupling partners, including those that allow construction of challenging 1,1-diaryl quaternary stereocentres. Biochemical, structural and computational studies provide insights into the catalytic mechanism of S(N)Ar1.3, including the emergence of a halide binding pocket shaped by key catalytic residues Arg124 and Asp125. This study brings a landmark synthetic reaction into the realm of biocatalysis to provide an efficient and versatile platform for catalytic S(N)Ar chemistry. Engineered enzymes for enantioselective nucleophilic aromatic substitutions.,Lister TM, Roberts GW, Hossack EJ, Zhao F, Burke AJ, Johannissen LO, Hardy FJ, Millman AAV, Leys D, Larrosa I, Green AP Nature. 2025 Jan 15. doi: 10.1038/s41586-025-08611-0. PMID:39814071 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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