Allosteric change

Locher, K. P., Rees, B., Koebnik, R., Mitschler, A., Moulinier, L., Rosenbusch, J. P. and Moras, D. (1998). Transmembrane signaling across the ligand-gated FhuA receptor crystal structures of free and ferrichrome-bound states reveal allosteric changes, Cell, 95, 771-778. 

The architecture of various CYPs may accommodate entities of different shapes [139]. Several CYPs, particularly CYP3A4 [140,141] and CYP2C9 [142], may exhibit atypical (non-Michaelis-Menten) kinetics such as heterotropic activation, homotropic activation, substrate inhibition and partial inhibition, all in a substrate-effector-dependent manner [143]. Several hypotheses have been proposed to account for the observation of atypical kinetics, including simultaneous occupancy of the CYP active site by two substrates (or one substrate and one effector simultaneously) [144] and allosteric changes in CYP architecture due to binding of an effector [145,146]. Along... 

Allosteric changes usually involve rate-determining reactions. For example, glycolysis in the liver is stimulated following a meal by an increase in fructose 2,6-bisphosphate, an allosteric activator of phosphofructokinase (see p. 98). Gluconeogenesis is inhibited by fructose 2,6-bisphosphate, an inhibitor of fructose 1,6-bisphos-phatase (see p. 118). 

Mechano-ionoswitching takes place, for instance, in polytopic ligands presenting ion binding induced allosteric changes [8.201, 8.276] or when an ion binds to a catenand to form a catenate [8.281, 8.282]. Modulation of the binding of a second substrate may be brought about. 

Basani, R. B., D Andrea, G., Mitra, N., Vilaire, G., Richberg, M., Kowalska, M. A., Bennett, J. S., and Poncz, M. (2001). RGD-containing peptides inhibit fibrinogen binding to platelet alpha(IIb)beta 3 by inducing an allosteric change in the amino-terminal portion of alpha (lib). / Biol. Chem. 276, 13975-13981. 

The mechanism by which MTF-1 facilitates zinc-induction of metallothionein promoter through the MREs is not known, but several models have been proposed. First, zinc may act as a coinducer by binding to MTF-1 and creating an allosteric change, allowing MTF-1 to bind to the MREs. The model proposed for mammalian MTF-l/MRE interaction has already been proven for yeast copper metallothionein systems (Furst et al., 1988). Another possibility may be that, under normal conditions, an inhibitor binds MTF-1. When an influx of zinc occurs, MTF-1 binds the zinc, undergoes a conformational change and is released from the inhibitor. The protein would then have the ability to bind to the MREs. Finally, upon an increase in intracellular zinc concentration, a specific coactivator may bind zinc and interact with MTF-1 to maximally induce transcription. 

Allosteric (change) Alteration of protein conformation resulting in alteration of function (e.g., noncompetitive receptor inhibition). 

Serpins were first identified as a set of proteins able to inhibit proteases. The name serpin is derived from this activity serine protease inhibitors . Heparin is a mixture of polysaccharides that bind to antithrombin in, inducing an allosteric change that greatly enhances its inhibition of thrombin synthesis. Some surgical patients, especially those receiving hip or heart valve replacements and those at risk of ischemic stroke (clots in the brain), are given heparin. 

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