*Only looking for help with problem 5 or 6 please and thank you* Case 31 Hyperac
ID: 89700 • Letter: #
Question
*Only looking for help with problem 5 or 6 please and thank you*
Case 31 Hyperactive DNAse Variants: A Treatment for Cystic Fibrosis Focus concept Understanding the mechanism of action of an enzyme can lead to the construction of hyperactive variant enzymes with a greater catalytic efficiency than the wild type enzyme. Prcrcquisitcs Enzyme kinetics and inhibition. DNA structure. The hyperchromic effect. lhe properties of supercoiled DNA. Background The enzyme deoxyribonuclease I (DNA se is an endonuclease that hydrolyzes the phosphodiester bonds of the double-stranded DNA backbone to yield small oligonucleotide fragments. DNAse l is used therapeutically to treat patients with cystic fibrosis (CF) The DNAse I enzyme is inhaled into the lungs where it then acts upon the DNA contained in the viscous sputum secreted by the lungs in these patients. Hydrolysis of high molecular weight DNA to low molecular weight DNA in the sputum decreases its viscosity and improves lung function. Animal studies also have shown that DNAse I is effective in treating the autoimmune disease systemic lupus erythematosus (SLE). In this disease, the DNA secreted into the serum provokes an immune response. DNAse I prevents the immune response by degrading the DNA to smaller fragments that are not recognized by the immune system. Genentech, Inc., the company that produces the recombinant DNAse I, was interested in improving the efficiency of DNAse I so that less drug would be needed to achieve the same results. Scientists in the protein engineering lah constructed hyperactive variants at DNAse I which actually worked better than the wild-type enzyme. DNA se l acts by processively nicking the phosphodiester backbone, so the scientists reasoned that a variant that could create more nicks in a shorter period of time would act more efficiently than the wild-type enzyme. In this case, we will examine the engineered hyperactive variants and use the results to make some conclusions about the mechanism ofDNAse IExplanation / Answer
1(a) all structural variants have the replacement of positively charged amino acids.
1(b) because inserted positively charged amino acids interact with proximal negatively charged phosphate group of DNA
5.the data in the table shows that processivity inversely proportional to DNA concentration and DNA length.
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