3ZDN
D11-C mutant of monoamine oxidase from Aspergillus niger
Summary for 3ZDN
| Entry DOI | 10.2210/pdb3zdn/pdb |
| Descriptor | MONOAMINE OXIDASE N, 1,2-ETHANEDIOL, FLAVIN-ADENINE DINUCLEOTIDE, ... (4 entities in total) |
| Functional Keywords | oxidoreductase, flavin dependent oxidase, amines |
| Biological source | ASPERGILLUS NIGER |
| Cellular location | Peroxisome (Probable): P46882 |
| Total number of polymer chains | 4 |
| Total formula weight | 224858.72 |
| Authors | Frank, A.,Ghislieri, D.,Willies, S.,Turner, N.J.,Grogan, G. (deposition date: 2012-11-29, release date: 2013-10-09, Last modification date: 2023-12-20) |
| Primary citation | Ghislieri, D.,Green, A.P.,Pontini, M.,Willies, S.C.,Rowles, I.,Frank, A.,Grogan, G.,Turner, N.J. Engineering an Enantioselective Amine Oxidase for the Synthesis of Pharmaceutical Building Blocks and Alkaloid Natural Products. J.Am.Chem.Soc., 135:10863-, 2013 Cited by PubMed Abstract: The development of cost-effective and sustainable catalytic methods for the production of enantiomerically pure chiral amines is a key challenge facing the pharmaceutical and fine chemical industries. This challenge is highlighted by the estimate that 40-45% of drug candidates contain a chiral amine, fueling a demand for broadly applicable synthetic methods that deliver target structures in high yield and enantiomeric excess. Herein we describe the development and application of a "toolbox" of monoamine oxidase variants from Aspergillus niger (MAO-N) which display remarkable substrate scope and tolerance for sterically demanding motifs, including a new variant, which exhibits high activity and enantioselectivity toward substrates containing the aminodiphenylmethane (benzhydrylamine) template. By combining rational structure-guided engineering with high-throughput screening, it has been possible to expand the substrate scope of MAO-N to accommodate amine substrates containing bulky aryl substituents. These engineered MAO-N biocatalysts have been applied in deracemization reactions for the efficient asymmetric synthesis of the generic active pharmaceutical ingredients Solifenacin and Levocetirizine as well as the natural products (R)-coniine, (R)-eleagnine, and (R)-leptaflorine. We also report a novel MAO-N mediated asymmetric oxidative Pictet-Spengler approach to the synthesis of (R)-harmicine. PubMed: 23808566DOI: 10.1021/JA4051235 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.55 Å) |
Structure validation
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