Repressor enzyme

Richter PH, Eigen M. Diffusion controlled reaction rates in spheroidal geometry. Application to repressor operator association and membrane repressor enzymes. Biophys. Chem. 1974 2 255-263. 

Ans. Regulatory enzymes are present in each cell to prevent translation of most of the DNA messages in that particular cell. For example, heart cells do not need and must not synthesize the proteins found in brain cells or liver cells and so on. Repressor enzymes repress the synthesis of all proteins except those needed for the heart cell. Simultaneously, inducer enzymes induce the synthesis of proteins needed for the heart cell. Only about 2 percent of all the DNA in any cell is used for protein synthesis. 

For many years hemoglobin was the only allosteric protein whose stereochemical mechanism was understood in detail. However, more recently detailed structural information has been obtained for both the R and the T states of several enzymes as well as one genetic repressor system, the trp-repressor, described in Chapter 8. We will here examine the structural differences between the R and the T states of a key enzyme in the glycolytic pathway, phosphofructokinase. 

The trp repressor controls the operon for the synthesis of L-tryptophan in Escherichia coli by a simple negative feedback loop. In the absence of L-tryptophan, the repressor is inactive, the operon is switched on and the enzymes which synthesize L-tryptophan are produced. As the concentration of L-tryptophan increases, it binds to the repressor and converts it to an active form so that it can bind to the operator region and switch off the gene. 

More than 30 years ago Jacob and Monod introduced the Escherichia coli lac operon as a model for gene regulation. The lac repressor molecule functions as a switch, regulated by inducer molecules, which controls the synthesis of enzymes necessary for E. coli to use lactose as an energy source. In the absence of lactose the repressor binds tightly to the operator DNA preventing the synthesis of these enzymes. Conversely when lactose is present, the repressor dissociates from the operator, allowing transcription of the operon. 

A review is given of the application of Molecular Dynamics (MD) computer simulation to complex molecular systems. Three topics are treated in particular the computation of free energy from simulations, applied to the prediction of the binding constant of an inhibitor to the enzyme dihydrofolate reductase the use of MD simulations in structural refinements based on two-dimensional high-resolution nuclear magnetic resonance data, applied to the lac repressor headpiece the simulation of a hydrated lipid bilayer in atomic detail. The latter shows a rather diffuse structure of the hydrophilic head group layer with considerable local compensation of charge density. 

Soft rot symptoms produced by E. chrysanthemi consist of a disorganisation of parenchymatous tissues following the release of bacterial pectinolytic enzymes. The diverse enzymes do not contribute equally to the virulence on a given host and their implication may vary according to the host considered. For instance, inactivation of pelE, pelD, pelA or pern in strain 3937 considerably reduces the virulence on African violets while mutations in pelB or pelC remain ineffective [2]. Pectinolysis is regulated by the transcriptional repressor KdgR, inactive in the presence of pectic inducers. 

The temperate virus does not exist in its mature, infectious state inside the cell, but rather in a latent form, called the provirus or prophage state. In considering virulent viruses we learned that the DNA of the virulent virus contains information for the synthesis of a number of enzymes and other proteins essential to virus reproduction. The prophage of the temperate virus carries similar information, but in the lysogenic cell this information remains dormant because the expression of the virus genes is blocked through the action of a specific repressor coded for by the virus. As a result of a genetic switch, the repressor is inactivated, virus reproduction occurs, the cell lyses, and virus particles are released. 

The Lac operon is made up of three genes (designated A, Y and Z), which code for enzymes which metabolize lactose and the control element whose function is to activate transcription of the A,Y and Z genes. Normally (i.e. when there is sufficient glucose available), a protein called a repressor blocks the control element and so the A, Y and Z genes are off. 

When lactose but not glucose is available, a chemical derivative of the disaccharide binds to the repressor, changing its shape. This in turn prevents the repressor binding to the control element. Once the control element is open , it directs the expression of the A, Y and Z genes which leads to the production of the enzymes which allow the efficient utilization of the lactose. 

Chen, P., Johnson, P., Sommer, T., Jentsch, S., and Hochstrasser, M. Multiple ubiquitin-conjugating enzymes participate in the in vivo degradation of the yeast MATa2 repressor. Cell 1993, 74, 357-69. 

Answer E. The decrease in enzyme activity is caused by the depletion of lactose, its dissociation from the repressor protein, and binding of the repressor to the operator control region. 

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