Molecular basis of allosteric activation of bacterial L-lactate dehydrogenase.
The three-dimensional structure of allosteric L-lactate dehydrogenase from Bifidobacterium longum, the first example of a T-state structure of L-lactate dehydrogenase, has been determined to 2.0 A. A comparative study of this structure with the previously reported R-state structure from Bacillus stearothermophilus has revealed the allosteric activation mechanism of the bacterial L-lactate dehydrogenase. The fructose 1,6-bisphosphate-induced conformational change at the effector site and the substrate affinity change at the activity site are clearly shown at a molecular level. Coupling of these changes can be simply explained by a set of concerted rotations between subunits in the tetramer of the enzyme. This T to R transition is the first example for a tetrameric allosteric protein where the rotations occur around each of three axes of symmetry.
Iwata
S
S
Photon Factory, National Laboratory for High Energy Physics, Ibaraki-ken, Japan.
Ohta
T
T
D000494:Allosteric Regulation; D001644:Bifidobacterium / Q000201:enzymology*; D001665:Binding Sites; D003461:Crystallography; D004789:Enzyme Activation; D005635:Fructosediphosphates / Q000494:pharmacology; D007770:L-Lactate Dehydrogenase / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure; D008958:Models, Molecular; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D013431:Sulfates / Q000737:chemistry
D005635:Fructosediphosphates; D013431:Sulfates; D007770:L-Lactate Dehydrogenase; C029063:fructose-1,6-diphosphate