7E0X
Crystal structure of Arabidopsis thaliana HPPD complexed with 4-hydroxyphenylacetic acid
Summary for 7E0X
| Entry DOI | 10.2210/pdb7e0x/pdb |
| Descriptor | 4-hydroxyphenylpyruvate dioxygenase, COBALT (II) ION, 4-HYDROXYPHENYLACETATE, ... (4 entities in total) |
| Functional Keywords | enzyme, complex, intermediate product, oxidoreductase |
| Biological source | Arabidopsis thaliana (Mouse-ear cress) |
| Total number of polymer chains | 1 |
| Total formula weight | 44995.41 |
| Authors | Lin, H.Y.,Yang, G.F. (deposition date: 2021-01-28, release date: 2021-12-08, Last modification date: 2024-10-16) |
| Primary citation | Lin, H.Y.,Chen, X.,Dong, J.,Yang, J.F.,Xiao, H.,Ye, Y.,Li, L.H.,Zhan, C.G.,Yang, W.C.,Yang, G.F. Rational Redesign of Enzyme via the Combination of Quantum Mechanics/Molecular Mechanics, Molecular Dynamics, and Structural Biology Study. J.Am.Chem.Soc., 143:15674-15687, 2021 Cited by PubMed Abstract: Increasing demands for efficient and versatile chemical reactions have prompted innovations in enzyme engineering. A major challenge in engineering α-ketoglutarate-dependent oxygenases is to develop a rational strategy which can be widely used for directly evolving the desired mutant to generate new products. Herein, we report a strategy for rational redesign of a model enzyme, 4-hydroxyphenylpyruvate dioxygenase (HPPD), based on quantum mechanics/molecular mechanics (QM/MM) calculation and molecular dynamic simulations. This strategy enriched our understanding of the HPPD catalytic reaction pathway and led to the discovery of a series of HPPD mutants producing hydroxyphenylacetate (HPA) as the alternative product other than the native product homogentisate. The predicted HPPD-Fe(IV)═O-HPA intermediate was further confirmed by the crystal structure of HPPD/S267W complexed with HPA. These findings not only provide a good understanding of the structure-function relationship of HPPD but also demonstrate a generally applicable platform for the development of biocatalysts. PubMed: 34542283DOI: 10.1021/jacs.1c06227 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.887 Å) |
Structure validation
Download full validation report
