In enzymology, 3-hydroxy-2-methylbutyryl-CoA dehydrogenase () is an enzyme that catalyzes the chemical reaction

The two substrates of this enzyme are (2S,3S)-2-methyl-3-hydroxybutyryrl-CoA and oxidised nicotinamide adenine dinucleotide (NAD+). Its products are 2-methylacetoacetyl-CoA, reduced NADH, and a proton.

This enzyme belongs to the family of oxidoreductases, specifically those acting on the CH-OH group of donor with NAD+ or NADP+ as acceptor. The systematic name of this enzyme class is (2S,3S)-3-hydroxy-2-methylbutanoyl-CoA:NAD+ oxidoreductase. Other names in common use include 2-methyl-3-hydroxybutyryl coenzyme A dehydrogenase, 2-methyl-3-hydroxybutyryl coenzyme A dehydrogenase, and 2-methyl-3-hydroxy-butyryl CoA dehydrogenase. This enzyme participates in valine, leucine and isoleucine degradation.

Structural studies As of 20 January 2010, 6 structure have been solved for this class of enzymes, with the PDB accession code , , , , , .

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