Name_________________________________________ Section_________ 7.012 Problem Set 1 Question 1 a) What are the four major types of biological molecules discussed in lecture? Give one important function of each type of biological molecule in the cell? b) Briefly answer the following questions. i) What are two main differences between prokaryotic cells and eukaryotic cells? ii) What is the difference between unicellular and multicellular organisms? iii) Are prokaryotes unicellular or multicellular? Are eukaryotes unicellular or multicellular? Question 1, continued c) For the pairs of amino acids given below circle each side chain. Give the strongest type of interaction that occurs between the side chain groups of each pair. d) Draw the chemical structure of the following polypeptide at pH 7. cysteine-alanine-tyrosine-phenylalanine e) In the structure that you drew above, circle a peptide bond. Question 2 The drug Minoxidil is used orally as an agent against hypertension and topically as a stimulant for hair growth. The structure if Minoxidil is shown. a) Below is a schematic of a Minoxidil binding site on a hypothetical protein. i) Draw the side chains at amino acid positions 51, 129, 134, and 167. ii) Draw Minoxidil as shown above binding in the site. Be sure to consider the interactions between Minoxidil and the side chains when orienting Minoxidil within the binding site. Question 2, continued b) List all the interactions that would occur between the specified amino acids and Minoxidil in the model you have proposed by filling out the table below. c) To decide if your model is correct, you construct some altered versions of this protein and test whether Minoxidil still binds. Assume all other amino acids remain unchanged. The results are as follows: Of the possible orientations for Minoxidil in the binding site, only one orientation is consistent with the results above. Please check your model carefully, revise it if needed and answer the following questions. Explain in terms of your model and the likely interactions why... i) variant 2 will bind Minoxidil but variant 3 will not bind Minoxidil. ii) variant 5 will bind Minoxidil but variant 4 will not bind Minoxidil. Question 3 Growth factor receptors (shown below) are transmembrane proteins found on the cell surface. a) The majority of the molecules that constitute the above membrane belong to what class of macromolecules? ________________________________ Explain the important qualities/properties of these molecules that allow them to form membranes. Question 3, continued A smaller schematic of the growth factor receptor is shown here. b) Which stretch of amino acids in the above sequence is part of the transmembrane region of the receptor? Circle these amino acids and briefly explain your reasoning. When growth factor binds to the extracellular domain of the receptor, a conformational change occurs in the receptor. Growth factor binding causes dimerization of two adjacent receptors in the cell membrane. Upon dimerization, the intracellular domains of the receptors become activated. See schematic below. Question 3, continued c) Regions of the two receptors that interact upon dimerization are drawn below. In parts (i iv) below, name the strongest type of interaction (choose from; hydrogen bond, ionic, covalent, van der Waals) that occurs between the side chains of the amino acids indicated. d) Explain how Gln12 and Val98, which are far apart in the primary sequence of the protein, can be close to each other in the region of the protein diagrammed above. Question 3, continued e) Molecular interactions between the two receptors are important for dimerization. Thus, substitution of certain amino acids in the protein can affect receptor dimerization. Predict whether the receptors will or will not be able to dimerize given the substitutions (i - iv) below. EXPLAIN your reasoning. i) Asp68 Arg: ii) Ser53 Thr: iii) Phe50 Asn: iv) Val98 Ile: e) Substitution of one amino acid, Cys75 → Gly, leads to dimerization of the receptors with or without growth factor. Provide a brief explanation for this observation. Question 4 The following reaction is the tenth and final step in glycolysis: a) Calculate Keq for this reaction under standard conditions at 25oC, and circle the correct statement below. At equilibrium, [phosphoenolpyruvate] > [pyruvate] At equilibrium, [phosphoenolpyruvate] < [pyruvate] b) The following concentrations are found in red blood cells. Calculate G for the reaction at 37oC. In which direction will this reaction proceed spontaneously? [ADP] = 10 mM [ATP] = 81 mM [phosphoenolpyruvate] = 10 mM [pyruvate] = 500 mM Question 4, continued c) Draw the energy profile for this reaction under physiological conditions. On the diagram be sure to: 1) show relative energy levels of the reactants and the products. 2) label the axes 3) label reactants and products 4) indicate the energy of activation 5) indicate G d) How does pyruvate kinase (the enzyme that catalyzes this reaction) change the energy profile? STRUCTURES OF AMINO ACIDS at pH 7.0 For the reaction: Keq A + B C + D with Go as its standard free energy Enzyme Kinetics: 1 k3 ES For the enzyme catalyzed reaction: S + E E+P k k where: S = substrate E = enzyme P = product the reaction velocity is given by V= where: K M = 2 Vmax [S] K M + [S] k2 + k3 and: Vmax = k 3[E]total k1