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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 Energy Cost of dTTP Synthesis (Integrates with Chapter 20.) Starting from HCO3, glutamine, aspartate, and ribosc-5-P, how many ATP equivalents are consumed in the synthesis of dTTP in a eukaryotic cell, assuming dihydroorotate oxidation is coupled to oxidative phosphorylation? How does this result compare with the ATP costs of purine nucleotide biosynthesis calculated in problem 2?arrow_forwardPhosphoglycerate 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_forwardThe active site of lysozyme contains two amino acid residues essential for catalysis: Glu35 and Asp52. The pKa values of the carboxyl side chains of these residues are 5.9 and 4.5, respectively. What is the ionization state(protonated or deprotonated) of each residue at pH 5.2, the pH optimum of lysozyme? How can the ionization states of these residues explain the pH-activity profile of lysozyme shown below?arrow_forward
- Lysozyme 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_forwardWhat is the evidence that aspartate transcarbamoylase (ATCase) effects catalysis primarily by proximity? In the figure, what is the role of Lys 84' in the active site- interaction that appear to make with the substrate?arrow_forwardBacterial species that are capable of synthesising the amino acid histidine do not need it in their growth medium. Histidine biosynthesis requires a specific enzyme, which we shall refer to as histidine synthetase. When these bacteria are supplemented with histidine in their growth media, they cease intracellular histidine synthesis. Propose three distinct regulatory mechanisms to account for why histidine production ends when histidine is present in the growth medium. To further investigate this phenomena, you analyse the quantity of intracellular histidine synthetase protein produced when cells are cultured with and without histidine. The quantity of this protein is same in both scenarios. Which regulatory mechanism makes sense in light of this observation?arrow_forward
- Briefly describe the induced-fit conformational change when hexokinase binds its substrate.arrow_forwardResidue 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 (dipole-dipole interactions, hydrodgen bonds, London Dispersion Interactions, or Ion-Dipole Interactions) with the hydroxyl groups of the glucose substrate and can potentially function as either a (hydrogen bond donor and/or acceptor, hydrogen bond donor, or hydrogen bond acceptor) . The methyl group of Ala cannot participate in hydrogen bond formation, which explains the (increase or decrease)…arrow_forwardResidue 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_forward
- Propose 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_forwardThe 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_forwardA Leu →Ala mutation at a site buried in the core of the enzyme lysozymeis found to be destabilizing. Explain the observed effect of this mutationon lysozyme stability by predicting how enthalpy (ΔH°), conformationalentropy (ΔS°peptide), and the hydrophobic effect (ΔS°solvent) are expected to change for the mutant compared to wild-type lysozyme. Explain how ΔG°for unfolding is affected by your predicted changes in enthalpy or entropy.arrow_forward
BiochemistryBiochemistryISBN:9781305577206Author:Reginald H. Garrett, Charles M. GrishamPublisher:Cengage Learning