Allosteric regulation

In biochemistry, allosteric regulation is the regulation of an enzyme by binding an effector molecule at a site other than the enzyme's active site. The site to which the effector binds is termed regulatory site. Allosteric sites allow effectors to bind to the protein resulting in a conformational change involving protein dynamics. Effectors that enhance the protein's activity are referred to as allosteric activators, whereas those that decrease the protein's activity are called allosteric inhibitors. Allosteric regulations are a natural example of control loops, such as feedback from downstream products or feedforward from upstream substrates. Long-range allostery is important in cell signaling. Allosteric regulation is particularly important in the cell's ability to adjust enzyme activity; the term allostery comes from the Ancient Greek allos, "other", stereos, "solid". This is in reference to the fact that the regulatory site of an allosteric protein is physically distinct from its active site.

Many allosteric effects can be explained by the concerted MWC model put forth by Monod and Changeux, or by the sequential model described by Koshland and Filmer. Both postulate that protein subunits exist in one of two conformations, tensed or relaxed, that relaxed subunits bind substrate more than those in the tense state; the two models differ most in their assumptions about subunit interaction and the preexistence of both states. For proteins in which subunits exist in more than two conformations, the allostery landscape model described by Cuendet, LeVine, can be used; the concerted model of allostery referred to as the symmetry model or MWC model, postulates that enzyme subunits are connected in such a way that a conformational change in one subunit is conferred to all other subunits. Thus, all subunits must exist in the same conformation; the model further holds that, in the absence of any ligand, the equilibrium favors one of the conformational states, T or R. The equilibrium can be shifted to the R or T state through the binding of one ligand to a site, different from the active site.

The sequential model of allosteric regulation holds that subunits are not connected in such a way that a conformational change in one induces a similar change in the others. Thus, all enzyme subunits do not necessitate the same conformation. Moreover, the sequential model dictates that molecules of a substrate bind via an induced fit protocol. While such an induced fit converts a subunit from the tensed state to relaxed state, it does not propagate the conformational change to adjacent subunits. Instead, substrate-binding at one subunit only alters the structure of other subunits so that their binding sites are more receptive to substrate. To summarize: subunits need not exist in the same conformation molecules of substrate bind via induced-fit protocol conformational changes are not propagated to all subunits The morpheein model of allosteric regulation is a dissociative concerted model. A morpheein is a homo-oligomeric structure that can exist as an ensemble of physiologically significant and functionally different alternate quaternary assemblies.

Transitions between alternate morpheein assemblies involve oligomer dissociation, conformational change in the dissociated state, reassembly to a different oligomer. The required oligomer disassembly step differentiates the morpheein model for allosteric regulation from the classic MWC and KNF models. Porphobilinogen synthase is the prototype morpheein. Ensemble models of allosteric regulation enumerate an allosteric system's statistical ensemble as a function of its potential energy function, relate specific statistical measurements of allostery to specific energy terms in the energy function. Ensemble models like the ensemble allosteric model and allosteric Ising model assume that each domain of the system can adopt two states similar to the MWC model; the allostery landscape model introduced by Cuendet, LeVine allows for the domains to have any number of states and the contribution of a specific molecular interaction to a given allosteric coupling can be estimated using a rigorous set of rules.

Molecular dynamics simulations can be used to estimate a system's statistical ensemble so that it can be analyzed with the allostery landscape model. Allosteric modulation is used to alter the activity of molecules and enzymes in biochemistry and pharmacology. For comparison, a typical drug is made to bind to the active site of an enzyme which thus prohibits binding of a substrate to that enzyme causing a decrease in enzyme activity. Allosteric modulation occurs when an effector binds to an allosteric site of an enzyme and alters the enzyme activity. Allosteric modulators are designed to fit the allosteric site to cause a conformational change of the enzyme, in particular a change in the shape of the active site, which causes a change in its activity. In contrast to typical drugs, modulators are not competitive inhibitors, they can be positive causing an increase of the enzyme activity or negative causing a decrease of the enzyme activity. The use of allosteric modulation allows the control of the effects of specific enzyme activities.

In a biological system, allosteric modulation can be difficult to distinguish from modulation by substrate presentation. An example of this model is seen with the Mycobacterium tuberculosis, a bacterium, suited to adapt to l


Oldhamite is a calcium magnesium sulfide mineral with formula S. Ferrous iron may be present in the mineral resulting in the formula: S, it is a pale to dark brown accessory mineral in meteorites. It crystallizes in the cubic crystal system, but occurs as anhedral grains between other minerals, it was first described in 1862 for an occurrence in the Bustee meteorite, Uttar Pradesh, India. It was named for the Director of the Indian Geological Survey, it occurs as an interstitial mineral phase between silicate minerals in enstatite chondrite and achondrite meteorites. It occurs in association with enstatite, niningerite, troilite and calcite, it has been reported from a variety of meteorite locations around the world including the Allan Hills 84001 meteorite of Antarctica. It has been reported from a slag occurrence in France and a coal deposit in Poland. Glossary of meteoritics

Del Tenney

Delbert "Del" Tenney was an American actor, film director and film producer. Starting out as an actor he appeared in some Off-Broadway plays and performed in the Broadway premiere of Terence Rattigan's play Ross, he established a legacy in film with several low-budget horror/exploitation films in the 1960s, including The Horror of Party Beach. Based in Connecticut, Tenney's other films include Psychomania, The Curse of the Living Corpse, I Eat Your Skin. Tenney died on February 2013 at his home in Jupiter, Florida, he was 82. Tenney married stage and film actress Margot Hartman, they remained married until his death. Del Tenney on IMDb Del Tenney at the Internet Broadway Database Del Tenney at the Internet Off-Broadway Database Del Tenney at AllMovie