Describe the structure of glutamate How do you think guanidi

Describe the structure of glutamate. How do you think guanidinium group of TTX and glutamate in the channel become involve in the binding of TTX to the channel?

What is the Kd? what does it tell you about the binding of TTX to the Na- Channel?

Explain what is meant by an electrostatic interaction between two molecules. From what you know about these interactions, would you guess that the TTX effects on the channel are reversible or irreversible? Explain your answer

Explain how a conformation change in the channel complex might lead to tighter interactions between the TTX and the channel.

Solution

1. Glutamate is a non-essential aminoacid naturally occuring in L- form. The molecualr formula of glutamate is C₅H₈NO_4^-. IUPAC name is (2R)- 2-amino-5-hydroxy-5-oxopentonoate. TTX is neurotoxin, blocks voltage gated Na+ channels on the surface of nerve membranes. TTX contain positively charged guanidium group that contains 3 nitrogen atoms and pyrimidine ring which contains hydroxyl groups. These hydroxyl groups help in tighting the bond between TTX and cahnnel. The binding of TTX to the Na channels involves bond between positively charged guanidino group of TTX and negatively charged carboxyl group of gluatamate present at the mouth of Na+ channel.

2. Binding affinity is a strength of binding interaction. Binding affinity is measured by the equillibruim dissociation constant (K_d). The smaller the K_d value greater the binding affinty. Binding affinity is influenced by noncovalent intermolecular interactions like hydrogen bonding, electrostatic interactions. TTX mimics the hydrated Na cation enters the mouth of the Na- channel peptide complex binds to a peptide glutamate side group and further tightens it. The TTX and Na channel binding site is extremely tight.(K_d= 10 ^-10nm).

3. Electrostatic interaction is a interaction between or among anions and cations. These can be reversible or irreversible. The TTX irreversibly binds to the channel mimicing the hydrated sodium ions, blocks entry of Na+ ions.

4. The confirmational changes in the channel complex might lesd to tighter interactions between the TTX and the channel. Confirmations changes leads to smaller the dissociation constant so binding affinity increases. So the bond becomes tightens.