Interpretation:
About the chemistry of dTMP synthesis and the substrate-binding site of thymidylate synthase.
Concept introduction:
Thymidylate synthetase is an accelerator that catalyzes the conversion of deoxyuridine monophosphate (dUMP) to
Answer to Problem 15P
The balanced reaction is:
Explanation of Solution
The following are the reactions concerned within the conversion of UMP and
Taking away like products and reactants.
This leaves us with a net reaction.
The charged aspect chains of essential amino acid are wont to pull in negatively charged groups as seen within the catalyst thymidylate synthase. Note that Arg23 and Arg218 are on separate subunits than Arg178and Arg179.
The balanced reaction is:
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Chapter 26 Solutions
Biochemistry
- The enzymatic activity of lysozyme is optimal at pH 5.2 and decreases above and below this pH value. Lysozyme contains two amino acid residues in the active site essential for catalysis: Glu35 and Asp52. The pK value for the carboxyl side chains of these two residues are 5.9 and 4.5 respectively. What is the ionization state of each residue at the pH optimum of lysozyme? How can the ionization states of these 2 amino acid residues explain the pH-activity profile of lysozyme?arrow_forwardEquation 7a of the text, (Umax/KM1) [S] (v'max/KM2) [P] 1+ [S]/KM1 + [P]/KM2 - gives the expression for the rate of formation of product by a modified version of the Michaelis-Menten mechanism in which the second step is also reversible. Derive the expression and find its limiting behaviour for high and low concentrations of substrate.arrow_forwardPropose a mechanism for the conversion of Sadenosylmethionine into 1-aminocyclopropane-1-carboxylate (ACC) by ACC synthase, a PLP enzyme. What is the other product?arrow_forward
- Phosphoglycerate kinase shows induced fit resulting from the binding of both substrates to form the closed catalytic conformation. Maintainence of the closed conformation depends on the formation of a salt bridge between R62 and D200. What would be the effect of the mutation of D200 to the unusual amino acid shown below? Explain.arrow_forward. The mechanism for lysozyme cleavage of its polysaccharide substrate requires Glu35 in its nonionized form, whereas the nearby Asp52 must be ionized (see the figure below). The pK values for the side-chain carboxyl groups on the two amino acids in solution are virtually identical. a) How can one carboxyl group be charged and the other uncharged in the active site of lysozyme? b) The pH optimum for lysozyme is about 5. Why do you suppose that the activity decreases above and below this optimum? Glu3s NAG Asp52 0-H Glu35 -C Asp52 tri-NAG NAGarrow_forwardLysozyme is an enzyme that hydrolyzes bacterial cell wall polysaccharides. When this reaction is carried out in the presence of H218O, it is observed that there is retention of configuration at the C1 carbon of the D site sugar as shown below Two key amino acid side chains (an Asp and a Glu) essential for lysozyme’s catalytic activity are positioned above and below the C1-O bond that is cleaved as shown below. Suggest a plausible mechanism for the reaction that starts with a nucleophilic attack at C1.arrow_forward
- The S3’ pocket on PfSUB1 (attached) contains the side chains of Lys465 and Tyr427. Researchers discovered that the Km for substrates with acidic residues in the P3’ position are much lower than those with nonpolar resides at the P3’ position in PfSUB1. Explain the Km data.arrow_forwardEscherichia coli Fpg protein is responsible for removing damaged DNA base pairs such as C8-oxoguanine (8-oxoG). The catalytic mechanism is believed to involve the formation of a transient Schiff base intermediate formed between DNA base the N-terminal proline residue. Draw the structure of PTH-derivative that is formed after Fpg is subjected to one cycle of Edman degradation.arrow_forwardSynthesis of the purine nucleotides AMP andGMP proceeds by a branched pathway starting with ribose5-phosphate (R5P), as shown schematically in FigureQ3–4. Using the principles of feedback inhibition, proposea regulatory strategy for this pathway that ensures an ade-quate supply of both AMP and GMP and minimizes thebuildup of the intermediates (A–I) when supplies of AMPand GMP are adequate.arrow_forward
- Residue Asn 204 in the glucose binding site of hexokinase IV was mutated, in two separate experiments, to either Ala or Asp. The Asn → Ala mutant had a KM nearly 50-fold greater than the wild-type enzyme, and the Asn → Asp mutant had a 140-fold greater KM value than the wild-type enzyme. These mutations impact the intermolecular interactions between the enzyme and the glucose substrate.The amide functional group of the Asn side chain can form with the hydroxyl groups of the glucose substrate and can potentially function as either a . The methyl group of Ala cannot participate in hydrogen bond formation, which explains the in glucose affinity as indicated by the higher KM for the mutant enzyme. The side chain of Asp could potentially serve as a , but…arrow_forwardThe specific activity of a pure preparation of pyruvate kinase (PK) assayed in the direction of pyruvate formation (forward direction) is 220 U/mg at 25 C and at pH 7.5. This form of PK is a homotetramer (MW 240,000) with one active site per subunit. What is the kcat for PK in the forward direction?arrow_forwardLysozyme is an enzyme that hydrolyzes bacterial cell wall polysaccharides. When this reaction is carried out in the presence of H218O, it is observed that there is retention of configuration at the C1 carbon of the D site sugar as shown below: Would this result suggest that the enzyme mechanism involves the direct nucleophilic attack of water at C1 or that the enzyme mechanism involves attack by a nucleophilic amino acid side chain of the enzyme that generates a transient covalent intermediate?arrow_forward
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