• Dissociating Enzymes
• UMP Synthase
• Uridine Kinase
• Beta-alanine Synthase
• Purine & Pyrimidine Concentrations
A. Stabilizing the active conformation
Perhaps 80 - 90% of all enzymes form oligomers. A significant subset of these (perhaps 20%) has its ctivity controlled by readily inter-converting between the oligomeric species and the dissociated monomer. As shown for enzymes that have been studied in this laboratory, appropriate effector ligands promote a shift in the dissociatin equilibrium, by stabilizing the active or inactive conformations.
Change in activity accompanies association or dissociation. A number indicates the number of subunits in an oligomer; underlined number (i.e. 1) = native form of the enzyme (in the absence of effectors). Enzyme activity: green = most active; yellow = partly active; red = inactive. + = positive effector, one of the substrates; - = negative effector, an intermediate product or more distant end-product.
B. Catalytic site between subunits
In addition to promoting allosteric effects, such a flexible quaternary structure can also facilitate an additional degree of freedom in forming catalytic sites. If the protein subunit is so formed that a complete catalytic site is not properly defined, then the appropriate alignment of two subunits in a dimer may still achieve the needed ligand binding pockets.
Models for conformational change and loss of activity by dissociation. The middle dimeric species (a) is a transient intermediate form. In (b) the substrates A and B can only interact chemically when bound to the dimeric enzyme.
1. Yablonski, M. J., Pasek, D. A., Han, B.-D., Jones, M. E., & Traut, T. W. (1996) Intrinsic activity and stability of bifunctional UMP synthase, and of its two separate domains, orotate phosphoribosyl-transferase and orotidine-5'-phosphate decarboxylase. J. Biol. Chem.271, 10704-10708.
2. Traut, T.W. (1994) Dissociation of enzyme oligomers: A mechanism for allosteric regulation. CRC Crit. Rev. Biochem. Mol. Biol.29, 125-163.
3. Matthews, M.M., Liao, W., Kvalnes-Krick, K.L., and Traut, T.W. (1992) Beta-alanine Synthase: Purification and allosteric properties. Arch. Biochem. Biophys. 293, 254-263.