3) Histone deacetylases (HDACs) are zinc-dependent enzymes that catalyse the conversion of acetyllysine to lysine. HN HDAC NH₂ a) Propose the mechanism for the HDAC-catalysed reaction. b) What is the role of zinc ion in HDAC catalysis? c) Draw the pH-activity profile for HDAC-catalysed conversion of acetyllysine to lysine. Explain. d) Suggest two acetyllysine analogues that are substrates for HDACS. One should be a better substrate than acetyllysine, whereas the other one should be a worse substrate than acetyllysine. Explain. Mutations in the HDAC sequence could lead to a loss of the catalytic function. Which mutations are problematic? e) f) Lysine acetylation is a reversible reaction using acetyl-CoA as a co-substrate. Which coenzymes are required for synthesis of acetyl-CoA in nature? Propose the mechanism.

Biochemistry
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Chapter1: Biochemistry: An Evolving Science
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3) Histone deacetylases (HDACs) are zinc-dependent enzymes that catalyse the conversion of
acetyllysine to lysine.
e)
HN
a) Propose the mechanism for the HDAC-catalysed reaction.
b) What is the role of zinc ion in HDAC catalysis?
c)
d)
f)
HDAC
NH₂
Draw the pH-activity profile for HDAC-catalysed conversion of acetyllysine to lysine.
Explain.
Suggest two acetyllysine analogues that are substrates for HDACs. One should be a better
substrate than acetyllysine, whereas the other one should be a worse substrate than
acetyllysine. Explain.
Mutations in the HDAC sequence could lead to a loss of the catalytic function. Which
mutations are problematic?
Lysine acetylation is a reversible reaction using acetyl-CoA as a co-substrate. Which
coenzymes are required for synthesis of acetyl-CoA in nature? Propose the mechanism.
Transcribed Image Text:3) Histone deacetylases (HDACs) are zinc-dependent enzymes that catalyse the conversion of acetyllysine to lysine. e) HN a) Propose the mechanism for the HDAC-catalysed reaction. b) What is the role of zinc ion in HDAC catalysis? c) d) f) HDAC NH₂ Draw the pH-activity profile for HDAC-catalysed conversion of acetyllysine to lysine. Explain. Suggest two acetyllysine analogues that are substrates for HDACs. One should be a better substrate than acetyllysine, whereas the other one should be a worse substrate than acetyllysine. Explain. Mutations in the HDAC sequence could lead to a loss of the catalytic function. Which mutations are problematic? Lysine acetylation is a reversible reaction using acetyl-CoA as a co-substrate. Which coenzymes are required for synthesis of acetyl-CoA in nature? Propose the mechanism.
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