T and R states in the crystals of bacterial L-lactate dehydrogenase reveal the mechanism for allosteric control.
The crystal structure of L-lactate dehydrogenase from Bifidobacterium longum, determined to 2.5 A resolution, contains a regular 1:1 complex of T- and R-state tetramers. A comparison of these two structures within the same crystal lattice and kinetical characterization of the T-R transition in solution provide an explanation for the molecular mechanism of allosteric activation. Substrate affinity is controlled by helix sliding between subunits which is triggered by the binding of the activator, fructose 1,6-bisphosphate. The proposed mechanism can explain activation by chemical modification and mutagenesis, as well as suggesting why vertebrate counterparts are not allosteric.
Iwata
S
S
Department of Agricultural Chemistry, University of Tokyo, Japan.
Kamata
K
K
Yoshida
S
S
Minowa
T
T
Ohta
T
T
D000494:Allosteric Regulation; D001644:Bifidobacterium / Q000201:enzymology; D001665:Binding Sites; D018360:Crystallography, X-Ray; D004789:Enzyme Activation; D005635:Fructosediphosphates / Q000737:chemistry; D007700:Kinetics; D007770:L-Lactate Dehydrogenase / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D011487:Protein Conformation; D013379:Substrate Specificity
D005635:Fructosediphosphates; D007770:L-Lactate Dehydrogenase; C029063:fructose-1,6-diphosphate