Hello. My name is Seva Katrich and I'm
a computational biologist and a computational chemist from
The Bridge Institute and Michelson Center for
Convergent Bioscience at the University of Southern California in Los Angeles.
So, today, we're going to talk about conserved allosteric sodium ions in class A GPCRs.
The brief outline of the talk today-
we'll discuss conserved sodium sites from a structural perspective.
We'll discuss early evidence for selective sodium allosteric effects in GPCRs.
We'll describe a theory or hypothesis for
sodium as a key allosteric cofactor in GPCR signaling mechanisms.
I will describe some current studies on
sodium dynamics and potential for sodium site protonation.
We'll also touch a little bit about our attempts for
practical applications from the knowledge about sodium site,
including mutations of sodium pocket and
including design of bitopic ligand targeting sodium pocket,
and then I will give a brief summary.
A little bit of an introduction of GPCRs in human biology and pharmacology.
As you're well aware,
there are more than 800 G-protein-coupled receptors
and they are omnipresent in our human body.
They're involved in all signaling systems as neurotransmitters.
You can see some familiar names like adrenaline,
dopamine, ligands that activate corresponding G-protein-coupled receptors
and they react to hormones and neuropeptides.
They're involved in the immune system, in embryo development,
and in practically all sensory functions of the human body.
Not surprisingly, more than 30 percent of all drugs in clinics target GPCRs.
There are more than 120 established targets,
and basically, any G-protein-coupled receptor can be a target-
probably olfactory receptors are less targetable.
But, still, all chronic diseases especially,
including in the central nervous system,
so psychiatric or sleep disorders,
drug addiction, in the cardiovascular system,
in the endocrine, in the immune system,
they are targets for neurodegenerative and autoimmune disease and all the way to cancer.