6Z1K
A de novo Enzyme for the Morita-Baylis-Hillman Reaction BH32.6
Summary for 6Z1K
| Entry DOI | 10.2210/pdb6z1k/pdb |
| Descriptor | BH32.6 protein, DI(HYDROXYETHYL)ETHER, 1,2-ETHANEDIOL, ... (6 entities in total) |
| Functional Keywords | morita-baylis-hillman reaction, engineered, evolved, biosynthetic protein |
| Biological source | synthetic construct |
| Total number of polymer chains | 1 |
| Total formula weight | 27855.91 |
| Authors | Levy, C.W. (deposition date: 2020-05-13, release date: 2021-08-25, Last modification date: 2024-01-24) |
| Primary citation | Crawshaw, R.,Crossley, A.E.,Johannissen, L.,Burke, A.J.,Hay, S.,Levy, C.,Baker, D.,Lovelock, S.L.,Green, A.P. Engineering an efficient and enantioselective enzyme for the Morita-Baylis-Hillman reaction. Nat.Chem., 14:313-320, 2022 Cited by PubMed Abstract: The combination of computational design and directed evolution could offer a general strategy to create enzymes with new functions. So far, this approach has delivered enzymes for a handful of model reactions. Here we show that new catalytic mechanisms can be engineered into proteins to accelerate more challenging chemical transformations. Evolutionary optimization of a primitive design afforded an efficient and enantioselective enzyme (BH32.14) for the Morita-Baylis-Hillman (MBH) reaction. BH32.14 is suitable for preparative-scale transformations, accepts a broad range of aldehyde and enone coupling partners and is able to promote selective monofunctionalizations of dialdehydes. Crystallographic, biochemical and computational studies reveal that BH32.14 operates via a sophisticated catalytic mechanism comprising a His23 nucleophile paired with a judiciously positioned Arg124. This catalytic arginine shuttles between conformational states to stabilize multiple oxyanion intermediates and serves as a genetically encoded surrogate of privileged bidentate hydrogen-bonding catalysts (for example, thioureas). This study demonstrates that elaborate catalytic devices can be built from scratch to promote demanding multi-step processes not observed in nature. PubMed: 34916595DOI: 10.1038/s41557-021-00833-9 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.48 Å) |
Structure validation
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