Calciseptine

Question 1

target of calciseptine

Answer 1

L-type ca2+ channel ONLY : predominantly found in heart, liver and smooth muscle

Question 2

Binding of calciseptine to the target

Answer 2

Binds to the 1,4-dihydropyridine binding site on the L-type calcium channel and physically block calcium from enetering

Question 3

L type calcium channel

Answer 3

‘Long lasting’ and require a strong depolarization for their activation ;
it is a macromolecular complex consisting of an ion-conducting protein (alpha 1 subunit) and additional accessory peptided with regulatory function ( alpha2delta, and beta 1-4 and gamma subunit)

Question 4

structure of calciseptine

Answer 4

three-finger toxin; 60 amino acids, 4 disulfide bond; core alpha1 subunit, intracellular beta subunit and extracellular alpha 2 subunit
use proline flanking to identify the site of protein protein interaction in calciseptine - residue 43-46

Question 5

function of calciseptine

Answer 5

act as agonist; share similar properties with 1,4-dihydropyridine derivatives (which is used for cardiovascular diseases such as hypertension)

Question 6

L-calchin

Answer 6

synthetic 8 residue peptide; similar to calciseptine; within the 8 residue, there is the the binding site; injection of L-calchin reduced systolic bp peak, reducing bp but did not affect diastolic bp and heart rate.
L-calchin resulted in voltage-independent block of L-type Ca2+ channel currents = same properties as parents molecule calciseptine
but with lower potency.
This supported the identification of the site in calciseptine that is needed for p-p interactions
and reinforce the impt of proline bracket flanking

Question 7

Ca2+ level effects on cardio and skeletal muscle

Answer 7

Ca2+ level high, = cardiovascular muscle and smooth muscle contraction increases !
but the Ca2+ levels low = keep Na+ channels open ; more depolarization more firing of neurons (action potential initiation) leading to more contraction = spasm

Question 8

Toxin to therapeutics

Answer 8

smooth muscle relaxant and inhibitor of cardiac contractions
Clinical features of CCB poisoning include hypotension, bradycardias, conduction blocks, pulmonary edema, hyperglycemia and metabolic acidosis

Question 9

Proline flanking technology

Answer 9

• Proline are usually found near sites of protein protein interaction
• The probability of finding a proline in site of interaction is 2.5 times higher than anywhere else.
• Proline is said to help protect the conformation and integrity of the interaction sites n to present the sites to their complementary proteins