9E97

L-allo-threonine aldolase from Thermotoga maritima N308E-Y87A-R122G-P121D Mutant with a 2-(aminomethyl)pyridine PLP modification

This is a non-PDB format compatible entry.

Summary for 9E97

• Entry DOI: 10.2210/pdb9e97/pdb
• Related: 9E9J
• Descriptor: L-allo-threonine aldolase, {5-hydroxy-6-methyl-4-[(E)-{[(pyridin-2-yl)methyl]imino}methyl]pyridin-3-yl}methyl dihydrogen phosphate, TETRAETHYLENE GLYCOL, ... (7 entities in total)
• Functional Keywords: pyridoxal-5-phosphate, plp, enzyme, inhibitor complex, lyase
• Biological source: Thermotoga maritima
• Total number of polymer chains: 2
• Total formula weight: 78217.08

Authors

Wang, S.,Jeffrey, P.D.,Sorigue, D.,Hyster, T.K. (deposition date: 2024-11-07, release date: 2025-07-23, Last modification date: 2025-08-06)

Primary citation

Ouyang, Y.,Wang, S.,Sorigue, D.,Hyster, T.K.
Nucleophilic alpha-Functionalization of Benzyl Amines Using an Engineered Threonine Aldolase.
J.Am.Chem.Soc., 147:25184-25190, 2025

PubMed Abstract: Chiral amines are ubiquitous in pharmaceuticals and agrochemicals, making their efficient and selective synthesis a significant synthetic challenge. Threonine aldolases synthesize chiral amines via stereoselective C-C bond formation; however, they are restricted to small amino acids as pro-nucleophiles, limiting their utility in chemical synthesis. Here, we report an engineered threonine aldolase capable of α-functionalizing benzylamines. The evolved enzyme has excellent catalytic efficiency and accepts a broad range of (heterocyclic)benzyl amines and structurally diverse aldehydes to yield single-enantiomers of 1,2-amino alcohols in high-yield and diastereoselectivity. Mechanistic and crystallographic studies provide a rationale for how these mutations enable this previously unknown function. Moreover, beneficial mutations can be transferred to a related pyridoxal-dependent protein, highlighting the generality of these insights.

PubMed: 40631863
DOI: 10.1021/jacs.5c04097

Experimental method

X-RAY DIFFRACTION (1.53 Å)