BCHM 10000 Lecture Notes - Lecture 21: Cellulase, Ribonuclease, Aromatic Amino Acids
27 Jun 2018
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Slide 1
Insecticides and nerve gases
• Organofluorophosphates are used as insecticides and nerve gases and are
irreversible inhibitors of the enzyme acetylcholinesterase
• Acetylcholinesterase breaks down acetylcholine in the synaptic cleft of
nerve junctions by hydrolyzing it to acetate and choline
• breakdown of acetylcholine attenuates nerve responses
BCHM 100 Weeks 10 -11
Blocks:
1. Chymotrypsin
2. Serine
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Slide 2
Acetylcholinesterase + sarin
•http://www.rcsb.org
• Search for “acetylcholinesterase”
• Scroll down and read the article about this enzyme.
• What are the 3 amino acids that form the “active site” of this enzyme (this is
the region where catalysis occurs)?
• What other enzymes also use this “catalytic triad” of amino acids?
• Nerve toxins and insecticides can inhibit this enzyme….find the PDB
structure showing this and download it and open in Pymol.
• Read the abstract about this structure. Which residue number is the active
site serine?
• Look back at the original article…what happens to this catalytic serine
residue when the enzyme is exposed to nerve gas such as sarin?
– Hint: click on the correct S residue in the sequence to highlight it and select
“sticks”. Then zoom in, and trace the peptide backbone so you can find the R
groups. What does the R group of this S look like?
– If you click on this extra “bit” on the Serine R group, what is highlighted in the
sequence? Look under ligand chemical component on the PDB page for this
structure to see what this is.
BCHM 100 Weeks 10 -11
find more resources at oneclass.com
find more resources at oneclass.com
Slide 3
Insecticides and nerve gases
• acetylcholinesterase inhibition results in prolonged nerve firing
•Atropine is an antidote for insecticide or nerve gas poisoning because it
blocks the binding of acetylcholine to its receptor
BCHM 100 Weeks 10 -11
find more resources at oneclass.com
find more resources at oneclass.com
Document Summary
Hint: click on the correct s residue in the sequence to highlight it and select. Then zoom in, and trace the peptide backbone so you can find the r groups. Look under ligand chemical component on the pdb page for this structure to see what this is. Insecticides and nerve gases acetylcholinesterase inhibition results in prolonged nerve firing: atropine is an antidote for insecticide or nerve gas poisoning because it blocks the binding of acetylcholine to its receptor. Insecticides and nerve gases: organofluorophosphates are irreversible enzyme inhibitors of many enzymes with active site serine residues. Enzyme is covalently modified after interaction with inhibitor. Modified enzyme is no longer a catalyst: organofluorophosphates form covalent product with active site serine residues (one residue actually) Mechanism and active site now known to be similar to those of acetylcholinesterase. Diisopropylfluorophosphate (difp) (an organofluorophosphate: the inhibitor becomes covalently bound to active site residues. Suggests what kind of chemistry is involved.
