Enzyme Inhibitors Flashcards
How do we classify enzymes?
Reversible or irreversible.
How do irreversible enzyme inhibitors bind?
They bind with a covalent bond.
Is penicillin reversible or irreversible?
Irreversible
What is the catalytic triad?
These are three amino acids that make up the catalytic site (active site) of many protease molecules.
What are the three catalytic triad AAs?
Serine, histidine, and glutamate
What is a mechanism of inhibition of the catalytic triad?
Phosphorylation. This is done by Paraoxon.
2-PAM reverses this phosphorylation, this is called the antidote.
What is the irreversible inhibitor of proteasome?
Carfilzomib
What causes the Carfilzomib to be irreversible?
The morpholino ring.
What are 5 examples of reversible inhibitors?
HIV Protease ACE HMG-CoA reductase cGMP Phosphodiesterase Calcineurin (a phosphatase)
What was the first proteasome inhibitor?
Bortezomib. It is a reversible inhibitor that is used to treat MM and cancer of plasma cells.
How does Bortezomib work?
It has boronic acid.
The boronic acid reacts with the hydroxyl group in the proteasome. It will bind to the serine or threonine residue in proteolytic enzymes.
What is Captopril?
A competitive ACE inhibitor that is reversible.
Where was bradykinin found?
It is a vasodilator that was found in snake venom.
ACE is a ____-containing protease
Zinc
What does LMTK3 do?
It is a regulator of ESR1. When it is active in promotes ESR1’s transcription, which leads to reistance to endocrine therapies in breast cancer.
LMTK3 also phosphorylates ERalpha, which contributes to Tamoxifen resistance and the phosphorylation protects ERalpha from ubiquitin-mediated degradation.
