4PA8
Crystal structure of a de novo retro-aldolase catalyzing asymmetric Michael additions, with a covalently bound product analog
Summary for 4PA8
| Entry DOI | 10.2210/pdb4pa8/pdb |
| Related | 4a29 4a2r 4a2s |
| Descriptor | retro-aldolase, (3R)-3-(4-methoxyphenyl)-5-oxohexanenitrile, SULFATE ION, ... (5 entities in total) |
| Functional Keywords | protein engineering, computer-aided design, aldolase, retro-aldolase, michael addition, enzyme design, directed evolution, substrate specificity, de novo protein, artificial catalyst, enzyme-product analog complex, tim-barrel fold, hydrolase |
| Biological source | Sulfolobus solfataricus |
| Total number of polymer chains | 1 |
| Total formula weight | 30517.03 |
| Authors | Beck, T.,Garrabou Pi, X.,Hilvert, D. (deposition date: 2014-04-07, release date: 2015-04-01, Last modification date: 2023-12-20) |
| Primary citation | Garrabou, X.,Beck, T.,Hilvert, D. A Promiscuous De Novo Retro-Aldolase Catalyzes Asymmetric Michael Additions via Schiff Base Intermediates. Angew.Chem.Int.Ed.Engl., 54:5609-5612, 2015 Cited by PubMed Abstract: Recent advances in computational design have enabled the development of primitive enzymes for a range of mechanistically distinct reactions. Here we show that the rudimentary active sites of these catalysts can give rise to useful chemical promiscuity. Specifically, RA95.5-8, designed and evolved as a retro-aldolase, also promotes asymmetric Michael additions of carbanions to unsaturated ketones with high rates and selectivities. The reactions proceed by amine catalysis, as indicated by mutagenesis and X-ray data. The inherent flexibility and tunability of this catalyst should make it a versatile platform for further optimization and/or mechanistic diversification by directed evolution. PubMed: 25777153DOI: 10.1002/anie.201500217 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.2 Å) |
Structure validation
Download full validation report
