7KC2

Symmetry in Yeast Alcohol Dehydrogenase 1 -Closed Form with NADH

Summary for 7KC2

• Entry DOI: 10.2210/pdb7kc2/pdb
• Related: 4W6Z 5ENV
• EMDB information: 22805
• Descriptor: Alcohol dehydrogenase, ZINC ION, NICOTINAMIDE-ADENINE-DINUCLEOTIDE, ... (4 entities in total)
• Functional Keywords: alcohol dehydrogenase, nadh complex, oxidoreductase
• Biological source: Saccharomyces cerevisiae (Baker's yeast)
• Total number of polymer chains: 4
• Total formula weight: 150176.27

Authors

Subramanian, R.,Chang, L.,Li, Z.,Plapp, B.V. (deposition date: 2020-10-04, release date: 2021-03-31, Last modification date: 2024-10-23)

Primary citation

Guntupalli, S.R.,Li, Z.,Chang, L.,Plapp, B.V.,Subramanian, R.
Cryo-Electron Microscopy Structures of Yeast Alcohol Dehydrogenase.
Biochemistry, 60:663-677, 2021

PubMed Abstract: Structures of yeast alcohol dehydrogenase determined by X-ray crystallography show that the subunits have two different conformational states in each of the two dimers that form the tetramer. Apoenzyme and holoenzyme complexes relevant to the catalytic mechanism were described, but the asymmetry led to questions about the cooperativity of the subunits in catalysis. This study used cryo-electron microscopy (cryo-EM) to provide structures for the apoenzyme, two different binary complexes with NADH, and a ternary complex with NAD and 2,2,2-trifluoroethanol. All four subunits in each of these complexes are identical, as the tetramers have 2 symmetry, suggesting that there is no preexisting asymmetry and that the subunits can be independently active. The apoenzyme and one enzyme-NADH complex have "open" conformations and the inverted coordination of the catalytic zinc with Cys-43, His-66, Glu-67, and Cys-153, whereas another enzyme-NADH complex and the ternary complex have closed conformations with the classical coordination of the zinc with Cys-43, His-66, Cys-153, and a water or the oxygen of trifluoroethanol. The conformational change involves interactions of Arg-340 with the pyrophosphate group of the coenzyme and Glu-67. The cryo-EM and X-ray crystallography studies provide structures relevant for the catalytic mechanism.

PubMed: 33620215
DOI: 10.1021/acs.biochem.0c00921

Experimental method

ELECTRON MICROSCOPY (2.67 Å)