7slh

Engineered sperm whale myoglobin-based carbene transferase MbBTIC-C3

spinqualitylabelsall models 7slh, resolution 1.15Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7slh is a 1 chain structure with sequence from Physeter catodon. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.15Å Ligands: HEM, SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function MYG_PHYMC Serves as a reserve supply of oxygen and facilitates the movement of oxygen within muscles. Publication Abstract from PubMed Catalysis with engineered enzymes has provided more efficient routes for the production of active pharmaceutical agents. However, the potential of biocatalysis to assist in early-stage drug discovery campaigns remains largely untapped. In this study, we have developed a biocatalytic strategy for the construction of sp(3)-rich polycyclic compounds via the intramolecular cyclopropanation of benzothiophenes and related heterocycles. Two carbene transferases with complementary regioisomer selectivity were evolved to catalyse the stereoselective cyclization of benzothiophene substrates bearing diazo ester groups at the C2 or C3 position of the heterocycle. The detailed mechanisms of these reactions were elucidated by a combination of crystallographic and computational analyses. Leveraging these insights, the substrate scope of one of the biocatalysts could be expanded to include previously unreactive substrates, highlighting the value of integrating evolutionary and rational strategies to develop enzymes for new-to-nature transformations. The molecular scaffolds accessed here feature a combination of three-dimensional and stereochemical complexity with 'rule-of-three' properties, which should make them highly valuable for fragment-based drug discovery campaigns. Biocatalytic strategy for the construction of sp(3)-rich polycyclic compounds from directed evolution and computational modelling.,Vargas DA, Ren X, Sengupta A, Zhu L, Roy S, Garcia-Borras M, Houk KN, Fasan R Nat Chem. 2024 May;16(5):817-826. doi: 10.1038/s41557-023-01435-3. Epub 2024 Feb , 13. PMID:38351380 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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