Allostery

Allostery is the key chemical process that makes possible intracellular and intercellular regulation . . the molecular interac-... 

Interestingly, their function is modified by many agents that allosterieally modify GABAa reeeptor funetion (e.g. barbiturates and steroids). A further parallel with the GABAa reeeptor is that there could well be differenees in subunit eomposition of 5-HT3 reeeptors sueh that different heteromerie eomplexes form reeeptors whieh are funetionally distinet. 

Ackers, G. (1998), Deciphering the molecular code of hemoglobin allostery , in Di Cera (Ed ), Advances in Protein Chemistry, Vol. 51, Linkage Thermodynamics of Macromolecular Interactions, Academic Press, San Diego, CA, pp. 185-253... 

See Monod (1971) this work also provides accessible and interesting accounts of the allostery and operon models. 

H. Frauenfelder, B.H. McMahon, R.H. Austin, K. Chu, and J.T. Groves, The role of structure, energy landscape, dynamics, and allostery in the enzymatic function of myoglobin. Proc. Natl. Acad. Sci. 98, 2370(2001). 

Allosteric enzymes show various activation and inhibition effects which are competitive in nature and related to conformational changes in the structure of the enzyme. Such allosteric enzymes are often crucial enzymes in metabolic pathways and exert control over the whole sequence of reactions. The name allostery refers to the fact that inhibition of the enzyme is by substances that are not similar in shape to the substrate. 

One excellent example of a Emax-type allosteric enzyme is Escherichia coli phosphoglycerate dehydrogenase (PGDH), a tetramer of identical subunits that catalyzes the formation of D-3-phosphohydroxypyruvate from D-3-phosphoglycerate in a reaction that uses NAD+ as a redox cofactor. This regulatory enzyme is allosteri-cally controlled by serine. All available information suggests that the effects on the for substrate are minor... 

HILL EQUATION PLOT ALLOSE KINASE ALLOSTERY... 

The ability of proteins to exist in different conformations is termed allostery (see 2.2). Allosteric enzymes can assume various conformations which differ in catalytic activity and/or substrate binding capacity. 

The symmetry model (fig. 2.4) of allostery can describe the cooperative binding of substrate to enzyme (homotropic effect), as well as the influence of effector molecules on the activity of enzymes (heterotropic effect). 

Fig. 2.4. The symmetry model of allostery. Shown here is the succesive binding of a hgand L to a protomer of a tetrameric protein with four ligand-binding sites according to the symmetry model. T tense form, R relaxed form.

Pan P., Woehl, E., Dunn, M.F. (1997) Protein architecture, dynamics and allostery in tryptophan synthase channeling. Trends Biochem, Sci, 22, 22-27. 

This behavior could easily be mistaken for half-of-the-sites reactivity, but all four sites appear to be independent.55,57 Coenzymes also bind independently to each site. In contrast, the enzyme from Bacillus stearothermophilus is allosteri-cally regulated.44,45 A tetrameric form is stabilized by the binding of two effector molecules of fructose 1,6-bisphosphate and binds pyruvate 50 times more tightly than the dimeric form does. The turnover numbers of tetramer and dimer are the same, and so they form a V-system (Chapter 8). The build up of the glycolytic intermediate fructose 1,6-bisphosphate under anaerobic conditions thus stimulates the regeneration of NAD+. 

Alternative models for hemoglobin allostery, (a) In the symmetry model hemoglobin can exist in only two states. (b) In the sequential model hemoglobin can exist in a number of different states. Only the subunit binding oxygen must be in the high-affinity form. 

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