Lecture 14: Hansen et al, 2005

Question 1

Which AchBP did they use?

Answer 1

One from the Aplysia Californica, which shares 33% homology with limnea. Needed to use non-glycosylated structure to get successful crystalization

Question 2

What are the nicotinic receptor agonists?

Answer 2

Nicotine, Ach, epibatidine (has bridge-ring structure), carbamylcholine (very similar to Ach), lobeline (partial agonist)

Question 3

What are the antagonists of Ach receptor?

Answer 3

methyllycaconitite (MLA), alpha-conotoxin ImI

Question 4

How are the alpha subunits oriented?

Answer 4

They are 11˚ more rotated in open position than the other subunits

Question 5

What are the interactions between lobeline and A-AchBP?

Answer 5

Trp147: H bond and cation pi bond with lob amine
other aromatics: Y195, Y55, Y188 point toward Lob amine
Lob C=O oxygens H bond with Trp147 N
Lob -OH H bond with Ser146

Question 6

What are the interactions between epibatidine and AchBP?

Answer 6

Trp147: H bonds and cation pi bond epi bridge ring
Y93, Y195, Y55 and Y188 point towards epi bridge ring amine

Cl hydrogen bonds to I106 and V108 carbonyl oxygens (must be binding to water first)