1: Proteins as drug targets Flashcards
which 4 drugs dont target proteins
antacids
osmotic diuretics
DNA modifying drugs
Membrane lipid targeting drugs
what is the main extracellular target protein
enzymes
main intracellular target proteins
nuclear hormone receptors
and
enzymes
what is binding domain
usually a acavity lined with amino acids that make up the protein
small part of the protein, so must ensure the binding energy that comes from the drug binding to it, has a conformational effect on the receptor
what are families and superfamilies based on
AA sequence similarity
what superfamily is the Estrogen like family part of
Nuclear hormone receptor superfamily
name the 4 subunits of estrogen receptors
androgen receptors
progesterone receptors
glucocorticoid receptors
mineralcorticoid receptors
general mechanism of NHR superfamily
bind lipohillic agonist
then regulate transcripstion of DNA
which causes changes in protein mexpression
what is an advantage of having multiple proteins that are tissue specific
the individual types ar especialised for each tissue
and if a disorder affects one protein, there’s only some functions that are affected instead of everything going to poo
also they can compensate for each other
where are corticosteroids produced
adrenal cortex
what are the natural steroids that bind to glucocorticoid (and mineralcorticoid undesireably)
hydrocortisone
corticosterone
what are 4 key receptors
Ligand-gated ion channel
Receptor tyrosine kinase
G protein-coupled receptors
nuclear hormone receptor
example of receptor tyronsine kinase
insulin receptor
what do RTKs bind
big molecules
peptide hormones
growth factors
cytokines
how do RTKs operate
recognise specfic AAs in target proteins
and phosphroyalte tyrosine residues in these target protein
G protein coupled receptor example
B2 adrenoceptor
what is the characteristic structure of the GPCR
3 transmembrane domains
whats name of enzyme that turns ATP into cyclic AMP
adenylate cyclase
which G protein stimulates and which inhibits adenylate cyclase
Gs stimulates
Gi inhibits
what pathway does Gq associate with
PIP2 pathway
when PIP2 is cleaved, what does this yield
DAG (Activates membrane targets)
and IP3 (intracellular soluble message, binds to Ca2+ stores -> which then can activate protein kinase C)
example of ligand gated ion channels
nicotinic Ach recpetor
what allows the LGIC to have so much diversity
multisubunit
so they can have many combinations
3 types of structures in LGIC
cys-loop receptors
iGlutamate receptors
P2X receptors
how many muscarinic acetylchloine receptors are there
5
what does the BetaGamma complex in G protein activate and inhibit
activates:
cardiac potassium channels
B-adrenoceptor kinase
inhibits:
calcium channels
3 main g proteins
Gi
Gs
and
Gq
3 subunits of Gi and the alpha subunits present
Gi - alpha i = inhibits adenylyl cyclase (AC)
Gt - alpha t (transducin) = activation of PDE-6 (vision)
Gg - alpha gust (gustducin) = activation of PDE-6 (taste)
2 subunits of Gs and the alpha subunits present
Gs - alpha s - activates AC
Golf - alpha olf - activates AC (olfaction)
whats the function of Gq subunit
phospholipase C activation
key players in adenylyl cyclase pathway
Gs or Gi
Adenylyl cyclase duh
ATP->cAMP
CNG/HCN channels
protein kinase A
key players in phospholipase C
Gq
phospholipase C
cleaves PIP2
DAG
IP3
Ca2+
protein kinase C
what 2 binding domains do NHRs have
DNA binding domain
and
ligand binding domain
what type of NHR is involved in transrepression
NHR monomer
what is an orphan receptor
Don’t know the function of some GPCRs and NHRs nor do we know their natural ligand
