TY - JOUR
T1 - Allosteric Control of Substrate Specificity of the Escherichia coli ADP-Glucose Pyrophosphorylase
AU - Ebrecht, Ana C
AU - Solamen, Ligin
AU - Hill, Benhamin L
AU - Iglesias, Alberto A
AU - Olsen, Ken W.
AU - Ballicora, Miguel A
PY - 2017/6/19
Y1 - 2017/6/19
N2 - The substrate specificity of enzymes is crucial to control the fate of metabolites to different pathways. However, there is growing evidence that many enzymes can catalyze alternative reactions. This promiscuous behavior has important implications in protein evolution and the acquisition of new functions. The question is how the undesirable outcomes of in vivo promiscuity can be prevented. ADP-glucose pyrophosphorylase from Escherichia coli is an example of an enzyme that needs to select the correct substrate from a broad spectrum of alternatives. This selection will guide the flow of carbohydrate metabolism toward the synthesis of reserve polysaccharides. Here, we show that the allosteric activator fructose-1,6-bisphosphate plays a role in such selection by increasing the catalytic efficiency of the enzyme toward the use of ATP rather than other nucleotides. In the presence of fructose-1,6-bisphosphate, the k cat/ S 0.5 for ATP was near ~600-fold higher that other nucleotides, whereas in the absence of activator was only ~3-fold higher. We propose that the allosteric regulation of certain enzymes is an evolutionary mechanism of adaptation for the selection of specific substrates.
AB - The substrate specificity of enzymes is crucial to control the fate of metabolites to different pathways. However, there is growing evidence that many enzymes can catalyze alternative reactions. This promiscuous behavior has important implications in protein evolution and the acquisition of new functions. The question is how the undesirable outcomes of in vivo promiscuity can be prevented. ADP-glucose pyrophosphorylase from Escherichia coli is an example of an enzyme that needs to select the correct substrate from a broad spectrum of alternatives. This selection will guide the flow of carbohydrate metabolism toward the synthesis of reserve polysaccharides. Here, we show that the allosteric activator fructose-1,6-bisphosphate plays a role in such selection by increasing the catalytic efficiency of the enzyme toward the use of ATP rather than other nucleotides. In the presence of fructose-1,6-bisphosphate, the k cat/ S 0.5 for ATP was near ~600-fold higher that other nucleotides, whereas in the absence of activator was only ~3-fold higher. We propose that the allosteric regulation of certain enzymes is an evolutionary mechanism of adaptation for the selection of specific substrates.
KW - allosteric regulation
KW - effectors interaction
KW - glycogen biosynthesis
KW - substrate promiscuity
UR - https://ecommons.luc.edu/chemistry_facpubs/109
U2 - 10.3389/fchem.2017.00041
DO - 10.3389/fchem.2017.00041
M3 - Article
VL - 5
JO - Chemistry: Faculty Publications and Other Works
JF - Chemistry: Faculty Publications and Other Works
IS - 41
ER -