8J5V
Crystal structure of estZF172 as a novel biocatalyst for the efficient biosynthesis of a chiral intermediate of pregabalin
Summary for 8J5V
| Entry DOI | 10.2210/pdb8j5v/pdb |
| Descriptor | Carboxylesterase (2 entities in total) |
| Functional Keywords | esterase/lipase family viii, carboxylesterase, lyase |
| Biological source | Pseudomonas putida (Arthrobacter siderocapsulatus) |
| Total number of polymer chains | 1 |
| Total formula weight | 44055.52 |
| Authors | Chi, C.B.,Liang, Z.D.,Huo, B.Q.,Hu, C.X.,Sun, Q.Y. (deposition date: 2023-04-24, release date: 2024-05-01, Last modification date: 2025-12-10) |
| Primary citation | Liang, Z.,Ma, X.,Sun, Q.,Zhang, X.,Wang, G.,Chi, C. Crystal Structure of EstZF172 Catalyzing Stereoselectively ( R )‐CNDE in Pregabalin Biosynthesis. Acs Omega, 10:21693-21700, 2025 Cited by PubMed Abstract: Pregabalin has garnered extensive clinical application for the management of neuropathic pain and epilepsy owing to its high efficacy and broad drug concentration range. EstZF172 is a key enzyme in the biosynthesis of pregabalin, capable of stereoselectively catalyzing the production of ()-CCMA from the key intermediate -CNDE. The novel crystal structure of EstZF172 indicates that it contains a highly conserved Ser-Lys-Tyr catalytic triad and belongs to the family VIII carboxylesterases. Molecular docking demonstrates that the steric hindrance presented by residues I159 and F239 plays a crucial role in influencing the binding affinity of the chiral substrate ()-CNDE for the catalytic site. The study provides a structural basis and reference for the stereoselective catalysis of EstZF172 and engineering modification of the key enzyme in the synthesis of pregabalin. PubMed: 40488026DOI: 10.1021/acsomega.5c01054 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.05 Å) |
Structure validation
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