Related Experiment Videos
Coenzyme-induced conformational changes and substrate binding in liver alcohol dehydrogenase
Ciba Foundation Symposium
|January 1, 1977
Summary
Liver alcohol dehydrogenase structures reveal how coenzyme binding changes protein conformation, shielding the active site. This structural insight is key to understanding enzyme function and substrate specificity in alcohol oxidation.
Area of Science:
- Biochemistry
- Structural Biology
- Enzymology
Background:
- Liver alcohol dehydrogenase (LADH) is crucial for alcohol metabolism.
- Understanding its structure is vital for elucidating its catalytic mechanism and substrate specificity.
Purpose of the Study:
- To determine the X-ray structures of apoenzyme and holoenzyme forms of LADH.
- To detail coenzyme binding, substrate specificity, and the catalytic mechanism.
Main Methods:
- X-ray crystallography was employed to resolve the three-dimensional structures.
- Crystals were formed from enzyme, coenzyme, and substrate/inhibitor mixtures.
Main Results:
- Coenzyme binding induces a conformational change, partially shielding the active site.
- A key hydrogen bond between Thr-178 and the coenzyme is essential for nicotinamide positioning.
- Substrates and inhibitors bind to the catalytic zinc atom within a hydrophobic pocket.
Conclusions:
- The LADH structure provides detailed insights into coenzyme binding and catalytic mechanisms.
- Zinc-mediated electrophilic catalysis is central to alcohol oxidation by LADH.