Sunday, 20 May 2012

Drugs That Target Shape Shifting Enzymes

A recent study has been undertaken at the Albert Einstein College of Medicine in Yeshiva University, New York, that takes a theory of enzyme reactions away from the drawing board and into the field. This study was carried out by Vern Schramm a professor in the department of Biochemistry at Yeshiva University.

Prof. Schramm’s research is advancement on a theory suggested in 1946 by Linus Pauling. Pauling suggested that an enzyme is at its most reactive state during a stage called ‘fleeting transition’. During this stage the enzyme will ‘shape-shift’ into its most reactive form, trigger the chemical reaction needed by the enzyme, then shift back to its original shape. With this information many scientists have claimed that if you were able to stop the chemical reaction caused by some harmful enzymes, for example Plasmodium falciparum which is the key enzyme in the malaria parasite, then you would be able to stop the corresponding disease. The only problem with this theory is that the fleeting transition stage happens in femtoseconds, that is, one millionth of a billionth of a second, for an easy comparative, a femtosecond is to a second what a second is to 31.7 million years. 
Diagram of an Enzyme

Schramm’s research is so vital because he has managed to make models of this reaction using molecular and computational techniques. With the help of these models Schramm has been able to create chemicals that can intercept the enzyme reaction at the fleeting transition state.  Once Schramm’s chemical has been introduced, it will fasten to multiple reactive forms of enzymes, fundamentally taking the enzymes out of action.

Andrew Murkin, a scientist that formerly worked with Schramm on his enzyme theories has recently taken the research into curing the lung disease tuberculosis. His major contribution to the progression of these drugs was in the discovery of the needed dosage to stop the enzyme from producing its catalytic duty. Murkin found that a low dosage of the drug could still provide the necessary blockage in enzyme functions. He says this is due to the accuracy of Schramm’s models and that this phenomenon of lower dosage equals equivalent reaction is usually only found in pharmacy by pure chance.

The most fascinating thing about Schramm’s research however would have to be his way around stopping mutations in diseases, therefore actually stopping the disease, not just a strand. This is due to the treatment Schramm is using; he is not targeting the disease specifically but instead targeting enzymes that trigger the disease. The greatest example of this is in his research in stopping the bacteria E.coli. With this experiment the communication enzyme was targeted, this left the bacteria with far less virulence. In practice this experiment has been shown to have the same effects on the 26th generations as it does on the first which is a great success in the fight against harmful bacteria.

Schramm’s research, in both theory and practice has made it possible for modern scientists to enter this one millionth of a billionth of a second quick reaction and impose their own outcomes. Schramm’s models have made it possible to not only stop a disease, like many antibiotics have been able to in the past, but also stop the mutation of a disease therefore stopping fatal diseases like leukaemia and malaria once and for all.

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