Allosteric control

Within glycolysis, the main allosteric control is exercised by phosphofructokinase, a complicated enzyme unusual in that its activity is stimulated by one of its products (ADP) and inhibited by one of its substrates (ATP). One further point about this enzyme which will be important to us later, in Aspergillus spp., elevated levels of ammonium ions relieve phosphofructokinase of inhibition by titrate. 

Nitrogen is normally supplied as an ammonium compound in dtric acid fermentations and suffident has to be supplied to enable the effect of manganese deficiency (increased levels of ammonium in the metabolic pool) to occur. Remember that increased metabolic pool ammonium has the effect of releasing the allosteric controls exerted on phosphofructokinase. 

Fig. 6.6 Tripodal polypeptide subject to allosteric control by Zn(ll) ions for the cleavage of RNA substrates [45]. The catalytic site with three Zn(ll) ions is the active species with HPNP, while the most active species with RNA is that devoid of metal ions...

Fructose 2,6-bisphosphate is formed by phosphorylation of fructose 6-phosphate by phosphofructoki-nase-2. The same enzyme protein is also responsible for its breakdown, since it has fructose-2,6-hisphos-phatase activity. This hifrmctional enzyme is under the allosteric control of fructose 6-phosphate, which stimulates the kinase and inhibits the phosphatase. Hence, when glucose is abundant, the concentration of fructose 2,6-bisphosphate increases, stimulating glycolysis by activating phosphofructokinase-1 and inhibiting... 

The wealth of data on HbSNO formation has given rise to two broad interpretations that either support the hypothesis that the S-nitrosation of Hb-Cys 93 is redox catalyzed by the heme and is under allosteric control or that it is N2 03 or N02 -mediated without the involvement of the hemes. 

Clearly, it would not be advantageous for synthesis and degradation to occur simultaneously, especially as they occur in the same cell compartment, the cytosol. Reciprocal control, that is when one enzyme is On the other is Off, is achieved via reversible phosphorylation of the key controlling enzyme and allosteric control (see Table 6.2 and Section 3.2.2). However, it is probable that both enzymes retain some residual activity at most times. 

The first phosphatase step is very important FBPase converts fructose,1-6-bisphos-phate into fructose-6-phosphate under allosteric control of several factors but during fasting, glucagon-induced regulation is crucial. One effect of glucagon stimulation of liver cells is to reduce the concentration of fructose-2,6-bisphosphate, an isomer that activates PFK-1 and is itself synthesized by PFK-2 when fructose-6-phosphate concentration rises... 

Subunit contacts need to be relatively extensive and stable if they are to ensure subunit association in the absence of a covalent link. However, in some cases a subunit contact can shift back and forth between two different stable positions, as has been demonstrated for oxy- versus deoxyhemoglobin (Perutz, 1970). Allosteric control can then be exerted by any factors which either affect the local conformation or bind between the subunits. A less elegant but even more extreme example is lamprey hemoglobin, which dissociates altogether in the oxy form (Hendrickson and Love, 1971). 

In a very broad overview of the structural categories one can state several statistical correlations with type of function. Hemes are almost always bound by helices, but never in parallel a//3 structures. Relatively complex enzymatic functions, especially those involving allosteric control, are occasionally antiparallel /3 but most often parallel a//3. Binding and receptor proteins are most often antiparallel /3, while the proteins that bind in those receptor sites (i.e., hormones, toxins, and enzyme inhibitors) are most apt to be small disulfide-rich structures. However, there are exceptions to all of the above generalizations (such as cytochrome cs as a nonhelical heme protein or citrate synthase as a helical enzyme), and when one focuses on the really significant level of detail within the active site then the correlation with overall tertiary structure disappears altogether. For almost all of the dozen identifiable groups of functionally similar proteins that are represented by at least two known protein structures, there are at least... 

Amino Acid Replacements for Allosteric Control in Crocodilian Hemoglobins ... 

Tahirov, T. H., Inoue-Bungo, T., Morii, H., Fujikawa, A., Sasaki, M., Kimura, K., Shiina, M., Sato, K., Kumasaka, T., Yamamoto, M., Ishii, S. and Ogata, K. (2001a). Structural analyses of DNA recognition by the AMLl /Runx-1 Runt domain and its allosteric control by CBFp. Cell 104,755-767. 

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