Thiazole-4-carboxamide adenine dinucleotide (TAD) is the active anabolite of the antitumor drug tiazofurin. β-methylene TAD (β-TAD) is a phosphodiesterase-resistant analogue of TAD, active in tiazofurin-resistant cells. β-methylene SAD (β-SAD) is the active selenium derivative of β-TAD. Both agents are analogues of the cofactor NAD and are capable of acting as general dehydrogenase inhibitors. Crystal structures of β-TAD and β-SAD bound to horse liver alcohol dehydrogenase (LADH) are presented at 2.9 and 2.7 Å, respectively. Both complexes crystallize in the orthorhombic space group C2221 and are isomorphous to apo-LADH. Complexes containing β-TAD and β-SAD were refined to crystallographic R values of 15% and 16%, respectively, for reflections between 8 Å and the minimum d spacing. Conformations of both inhibitors are similar. β-TAD and β-SAD bind to the “open” form of LADH in the normal cofactor- binding cleft between the coenyzme and catalytic domains of each monomer. Binding at the adenosine end of each inhibitor resembles that of NAD. However, the positions of the thiazole and selenazole heterocycles are displaced away from the catalytic Zn cation by ∼4 Å. Close intramolecular S-O and Se-O contacts observed in the parent nucleoside analogues are maintained in both LADH-bound β-TAD and β-SAD, respectively. These conformational constraints may influence the binding specificity of the inhibitors.