Drug Targets Flashcards
Transcription factors:
- promote or inhibit what?
- defining feature?
- what is the response element?
- promote or inhibit the recruitment of RNA polymerase to specific genes
- defining feature is the presence of the DNA-binding domain
- response element is the specific DNA sequence the TF binds to
GPCR ligands
Biogenic amines:
(x6)
acetylcholine, epinephrine, norepinephrine, dopamine, serotonin, histamine
GPCR ligands
Peptides/proteins:
(x4)
adrenocorticotropin, angiotensin, bradykinin, opioids
GPCR Ligands
Amino acids
glutamate, GABA
GPCR Ligands
Lipids
(x3)
leukotrienes, prostacyclin, TxA2
GPCR ligands
nucleotides
(x3)
adenosine, ADP, ATP
Structure of GPCR:
- transmembrane domain
- N terminal domain (extracellular) often is what?
- C-terminal domain (cytosolic) contains multiple what?
- cytoplasmic loops contain?
- 7 TM domain formed by a single polypeptide chain
- N-terminal domain is often glycosylated
- C-terminal domain contains multiple phosphorylation sites (serine/threonine residues)
- cytoplasmic loops contain G-protein binding sites
G-protein cycle:
-Six Steps
- basal unstimulated state
- Agonist activates receptor
- which promotes release of GDP from the G Protein
- Allows entry of GTP into nucleotide binding site
- Signal terminated by hydrolysis of GTP
- Return of system to (1)
Classification of G-protein families based on what?
based on Ga subunit-induced effects
Gs Gi Gq
-effect on adenylyl cyclase and Src tyrosine kinase
Gs activates all isoforms of adenylyl cyclase and Src tyrosine kinase
Gi inhibits adenylyl cyclases but activates tyrosine kinase Src
Gq activates phospholipase Cß
cAMP second messenger pathway
Ca2+-phosphoinositide signaling pathway
Receptors w/ Intrinsic Enzyme Activity:
(x6)
IGF-1, Insulin, VEGF, EGF, NGF, PDGF
Structure of RTKs
-exception to general rule
most RTKs possess a single polypeptide chain, but insulin and IGF receptors have 2 chains, alpha and beta, linked by a disulfide bond
-ligand-binding shows very little similarity between members of the family, but the tyrosine kinase domain is similar
Mechanism of activation of the epidermal growth factor receptor:
- what happens upon binding?
- what happens when cytoplasmic domain becomes phosphorylated?
- upon binding of EGF (circle), the receptor converts from its inactive monomeric state (left) to an active dimeric state (right), in which two receptor polypeptides bind noncovalently.
- the cytoplasmic domains become phosphorylated (P) on specific tyrosine residues (Y), and their enxymatic activities are activated, catalyzing phosphorylation of substrate proteins (S)