biochemistry/organic chemistry mechanizm

Name ______________________________________________ Problem 1. Enzyme A catalyzes the following reaction. A Lys residue in the active site was shown to take p[art in catalysis. Give a reasonable mechanism. (hint: the first step is attachment of one substrate to the enzyme via Schiff base formation). Problem 2.The following represents two steps in the breakdown of Trp. The first step removes the formyl group from the exocyclic amine and can occur via either hydrolytic or oxidative mechanism. Provide reasonable mechanisms for both, and then give a reasonable mechanism for the ring hydroxylation in the subsequent step. Problem 3. The following 2 compounds are mechanism-based inactivators of the aromatase enzyme (A cytochrome P450 that catalyzes deformylation of estrogen precursors). Give reasonable mechanisms for inactivation of the aromatase enzyme by each. Problem 4.The following compound inhibits a Glucosidase enzyme via irreversible inactivation. a. What 2 experiments would you carry out to determine what amino acid on the protein is covalently linked to the inhibitor. b. How could you determine if the labeled amino acid was, in fact, a part of the active site? Problem 5.Draw a reasonable mechanism for the conversion of compound A into the product B Problem 6. L-Aspartate can be decarboxylated to produce ?-alanine or ?-alanine. a. Draw a reasonable mechanism for each, including any likely cofactor involvement. b. Describe an experiment to test for each mechanism. Problem 7.An enzyme catalyzes the following reaction: Incubation of the enzyme with substrate along with [3H]NaBH4, followed by gel filtration gives a peak of radioactivity corresponding to the protein peak. Draw a mechanism consistent with this result Problem 8. The enzyme catalyzing this reaction is PLP dependent. Give the mechanism. Problem 9.A single enzyme catalyzes all of the following reactions: Give a mechanism for each: In addition, draw a mechanism for the mechanism-based inactivation of this enzyme by ?-fluoroalanine: Problem 10. The carbon with the * below is derived from Serine. Show how this carbon ends up in the product invoking THF as a cofactor. Would you expect the fluorinated derivative below to be a mechanism-based inhibitor? Why or why not? Problem 11.For the following amino acid pairs A:B, predict the effect of A on the pKa of B if both groups are in close proximity in the active site: Your answers will be; “increase pKa” , “decrease pKa”, or “no effect” Problem 12. In the article by Adina-Zada et al., (Biochemistry 2014, 53, 1051-1058), what is the significance of the single turnover data shown in figure 3. What do these experiments contribute to the overall conclusions that were reached in the paper. This paper is posted in Canvas and is called “carboxyphosphate” Bonus: (5 points) You have discovered a novelprotein that catalyzes the key step in the biosynthesis of the miracle drug of the century. It appears to contain a novel cofactor that is covalently attached to the protein, but you propose this cofactor is actually generated from the protein sequence itself via an autocatalytic process. You determine the structure of this cofactor to be the following, where R1 is the amino terminus of the protein and R2 is the carboxy terminus. a. What is the key tripeptide sequence required for the synthesis of this cofactor? b. Give a reasonable mechanism for its formation. (hint: there are 4 key steps in the autocatalytic process)