7UQ9

S48T Horse Liver Alcohol Dehydrogenase in Complex with NADH and N-Cyclohexylformamide

Summary for 7UQ9

• Entry DOI: 10.2210/pdb7uq9/pdb
• Descriptor: Alcohol dehydrogenase E chain, ZINC ION, 1,4-DIHYDRONICOTINAMIDE ADENINE DINUCLEOTIDE, ... (5 entities in total)
• Functional Keywords: ternary complex, oxidoreductase
• Biological source: Equus caballus (horse)
• Total number of polymer chains: 2
• Total formula weight: 81951.85

Authors

Zheng, C.,Boxer, S.G. (deposition date: 2022-04-19, release date: 2023-02-01, Last modification date: 2023-12-13)

Primary citation

Zheng, C.,Ji, Z.,Mathews, I.I.,Boxer, S.G.
Enhanced active-site electric field accelerates enzyme catalysis.
Nat.Chem., 15:1715-1721, 2023

PubMed Abstract: The design and improvement of enzymes based on physical principles remain challenging. Here we demonstrate that the principle of electrostatic catalysis can be leveraged to substantially improve a natural enzyme's activity. We enhanced the active-site electric field in horse liver alcohol dehydrogenase by replacing the serine hydrogen-bond donor with threonine and replacing the catalytic Zn with Co. Based on the electric field enhancement, we make a quantitative prediction of rate acceleration-50-fold faster than the wild-type enzyme-which was in close agreement with experimental measurements. The effects of the hydrogen bonding and metal coordination, two distinct chemical forces, are described by a unified physical quantity-electric field, which is quantitative, and shown here to be additive and predictive. These results suggest a new design paradigm for both biological and non-biological catalysts.

PubMed: 37563323
DOI: 10.1038/s41557-023-01287-x

Experimental method

X-RAY DIFFRACTION (1.4 Å)