PDE3 is a phosphodiesterase. The PDEs belong to at least eleven related gene families, which are different in their primary structure, substrate affinity, responses to effectors, and regulation mechanism. Most of the PDE families are composed of more than one gene. PDE3 is clinically significant because of its role in regulating heart muscle, vascular smooth muscle and platelet aggregation. PDE3 inhibitors have been developed as pharmaceuticals, but their use is limited by arrhythmic effects and they can increase mortality in some applications.
The mammalian PDEs share a common structural organization and contain three functional domains, which include the conserved catalytic core, a regulatory N-terminus, and the C-terminus. The conserved catalytic core is much more similar within PDE families, with about 80% amino acid identity, than between different families. It is believed that the core contains common structural elements that are important for the hydrolysis of cAMP and cGMP phosphodiester bonds. It is also believed that it contains family-specific determinants for differences in affinity for substrates and sensitivity for inhibitors.
The catalytic domain of PDE3 is characterized by a 44-amino acid insert, but this insert is unique to the PDE3 family, and is a factor when determining a structure for a potent and selective PDE3 inhibitor.
The crystal structure of the catalytic domains of several PDEs, including PDE3B, have shown that they contain three helical subdomains :
Push up
Haha, I never knew that a kid like me
Could take his mic around the world
(World)
Flash the big S.D.
And rock the masses
From Madrid to Calabasas
Tijuana, Mexico
Bootleg demos in Tokyo
Say they know me though
'Cause I'll be puttin' in work
Commit my life to rebirth
Well respected, 'cause that's my word
And I'm sure you heard
(Heard)
'Bout a new sound goin' 'round
She might have left my hood
But she was born in my town
You didn't know, thought we was new on the scene
(Well it's alright, it's alright)
I know you know, I see you smilin' at me
(Well it's alright, it's alright)
Boom!
Here comes the
Boom!
Ready or not?
Here comes the boys from the South
Boom!
Here comes the
Boom!
Ready or not?
How you like me now?, I say
We rep the South
So what you talkin' 'bout?
I'm not runnin' off my mouth
I know this without a doubt
'Cause if you know these streets
Then these streets know you
An' when it's time to handle business
Then you know what to do
(What to do)
Me and my crew
We stay true, old skool or new
Many were called
But the chosen are few
(We are few)
We rise to the top
What you want, just in case you forgot
Rush the stage, grab my mic
Show me what you got?
You didn't know, thought we was new on the scene
(Well it's alright, it's alright)
I know you know, I see you smiling at me
(Well it's alright, it's alright)
Boom!
Here comes the
Boom!
Ready or not?
Here comes the boys from the South
Boom!
Here comes the
Boom!
Ready or not ?
How you like me now?, I say
Boom!
Here comes the
Boom!
Ready or not?
Here comes the boys from the South
Boom!
Here comes the
Boom!
Ready or not?
How you like me now?
Is that all you got?, haha
I'll take your best shot
Is that all you got?, ha ha
I'll take your best shot
Is that all you got?, I'll take your best shot
Is that all you got?, I'll take your best shot
Is that all you got?, I'll take your best shot
I'll take your best shot, I'll take your best shot
Is that all you got?
(Well it's alright, it's alright)
I'll take your best shot
Is that all you got?
(Well it's alright, it's alright)
I'll take your best shot
Is that all you got?, I'll take your best shot
(Well it's alright, it's alright)
Take your best shot, take your best shot
Is that all you got?, I'll take your best shot
(Well it's alright, it's alright)
Take your best shot, take your best shot
Boom!
Here comes the
Boom!
Ready or not?
Here comes the boys from the South
Boom!
Here comes the
Boom!
Ready or not?
Haha, how you like me now?, I say
Boom!
Here comes the
Boom!
Ready or not?
Here comes the boys from the South
Boom!
Here comes the
Boom!
Ready or not?