Eklund H, Brändén C I
J Biol Chem. 1979 May 10;254(9):3458-61.
The three-dimensional structure of a ternary complex of horse liver alcohol dehydrogenase with reduced nicotinamide adenine dinucleotide and the inhibitor dimethyl sulfoxide has been determined to 4.5 A resolution independently of the apoenzyme structure. The electron density maps of both structures have been compared. The two coenzyme binding domains which form the center of the dimer molecular have retained their conformation and orientation within the molecule whereas the catalytic domains rotate and narrow the cleft between the domains. The active site becomes shielded from the solution by a combination of this rotation, local movements of a loop from residues 53 to 57 and coenzyme and substrate binding. Both subunits bind coenzyme and inhibitor to the same extent. The nicotinamide ring of the coenzyme is positioned close to the active zinc atom and the inhibitor is bound to this zinc atom. The difference between the two crystallographically independent subunits is small. The proposed mechanisms of action for the enzyme based on the apoenzyme structure are confirmed by the present investigation.
已独立于脱辅酶结构，将马肝醇脱氢酶与还原型烟酰胺腺嘌呤二核苷酸及抑制剂二甲亚砜的三元复合物的三维结构解析至4.5埃分辨率。已比较了这两种结构的电子密度图。形成二聚体分子中心的两个辅酶结合结构域在分子内保持了它们的构象和取向，而催化结构域发生旋转并使结构域之间的裂隙变窄。通过这种旋转、53至57位残基形成的环的局部移动以及辅酶和底物结合的共同作用，活性位点被与溶液隔离开来。两个亚基结合辅酶和抑制剂的程度相同。辅酶的烟酰胺环靠近活性锌原子定位，且抑制剂与该锌原子结合。两个晶体学独立亚基之间的差异很小。本研究证实了基于脱辅酶结构提出的该酶作用机制。
