Allosteric Regulation
Allosteric regulation is a process that takes place when regulatory triggers, like the binding of a small molecule inhibitor, takes place in another location other than the active site of the protein. Many proteins undergo this kind of regulation and show various mechanisms of allosteric control. Because of this regulation, the active site changes in shape, thereby preventing the substrate from binding. This create a significant impact on the activity of the enzyme.
The regulation of the function protein can be implemented at different stages in its life cycle, ranging from controlling gene expression to translation into protein to the eventual degradation. In fact, allosteric regulation is just one of the various regulations on protein function, although it plays a significant role in the process.
An overview of Allosteric Regulation
Allosteric controls can either increase or decrease the activity of proteins. This distinguishes it from a competitive inhibitor, whereby a small molecule inhibitor binds to the active site and blocks the natural ability of the protein to access the substrate. Another difference is that a competitive inhibition molecule may require chemical similarity to the substrate so as to step up the competition while an allosteric control does not.
Analyses of protein 3D structures has been instrumental in providing knowledge of allosteric mechanisms. In fact, there are more than 100 cases of proteins that experience allosteric control, whereby a structural model of either one, or both, of the active or dormant forms have been proven through experiments. The experiments can be done through X-ray crystallography or NMR spectroscopy.
When the structures are compared, they can offer suggestions on how the allosteric mechanism works. The following are some of the triggers and mechanisms that have been unearthed through the structural studies.
How Allosteric Regulation Operates
Two alternative models were identified for explaining the way in which an allosteric control works. Both alternatives relate to the assemblies of identical protein molecules or sub-sections by oligomeric protein. The assumption is that, every sub-section is either in a relaxed state (R) or tense state (T). Among the two, the R state has a higher receptive ability than the T state.
The Monod, Wyman and Changeux (MWC) model
According to the Symmetry or Monod, Wyman and Changeux (MWC) model, the sub-sections in every protein assembly must either all be in the R state or T state. This implies a confrontational alteration in one sub-section impacts similar changes in all the rest. The model explains the mechanism that works in various proteins, like hemoglobin, certain enzymes and membrane acceptors.
The Koshland, Nemethy and Filmer (KNF)
Also known as the sequential, in the KNF model, the sub-sections of every assembly do not all have to be in a similar state. The binding of a ligand to one sub-section takes place through induced fit, changing its confrontation from the T state to R state. This alteration affects the structures of adjacently positioned sub-sections, thereby giving them a higher receptive ability to ligand binding. However, the structures are not converted to the R state as seen in the symmetry model.
Allosteric Regulation by Small-molecule binding
The binding of small molecule inhibitors of effectors is the most common form of allosteric control. This experienced in most negative feedback loops of several biosynthetic pathways, whereby one of the pathways products prevents the further creation of the product through shutting down an enzyme involved in the early stages of the pathway. However, a pathway can also be activated if there is a specific molecule which switches on one of its critical enzymes.
Allosteric Regulation by Protein Binding
Proteins can also operate as allosteric inhibitors for other kinds of proteins. For instance, the role of cyclin-dependent kinase 2 (CDK2) is regulated through the binding of the protein cyclin. The CDK enzymes function as checkpoints in the cycle of eukaryotic cell and work by triggering the end targets through phosphorylation. For these enzymes to be switched on, the binding of the cyclin and phosphorylation by a CDK must take place.
Significance of Allosteric Regulation
Allosteric regulation ensures a higher degree of enzyme control than could be attained using inhibition or activation of an enzyme. The regulation can be effectively accomplished through enzymes and substrates concentration among other molecules that are not affected by the enzyme.
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References
http://www.sciencedirect.com/science/article/pii/S0014579309001926
http://study.com/academy/lesson/allosteric-regulation-of-enzymes-definition-significance.html
http://www.springer.com/cda/content/document/cda_downloaddocument/0602s.swf?SGWID=0-0-45-752220-0
http://www.els.net/WileyCDA/ElsArticle/refId-a0000865.html