Serotonin pictured below widely known as the happy chemical

Serotonin (pictured below), widely known as the \"happy chemical\", has been implicated in depression, mood regulation, social behavior, appetite, sleep, memory, as well as many others. It binds to a protein known as the 5-HT receptor. This receptor has a glutamate involved in keeping the serotonin bound in. When the glutamate is mutated to an aspartate, or separately to an isoleucine, the binding curves below are observed H2 glutamate Glu lle 0 Asp HN NH2 Serotonin Serotonin] Based on the structure of glutamate and the structure of serotonin, what kind of interactions would you expect to be involved in holding serotonin in place. The binding curve of serotonin with aspartate did not shift much, indicating the receptor has the same affinity for serotonin whether it uses aspartate or glutamate In thinking about the structure of all three, propose a hypothesis for this. Based on the binding curve above, does the receptor have a higher or lower affinity for serotonin when isoleucine is in place of glutamate? Suggest a theory to support this. a. b. c.

Solution

a) The binding interaction between serotonine and glutamate is Hydrogen bonds .The H-bonding interactions are formed between H of serotonine (N-H) and O of glutamate. The strong H-bonding is possible becuase of presence of a free carboxylate (-COO-) moiety in glutamate. Glutamate is an acidic amino acid containg two carboxylate and one ammonium moieties and the excess carboxylate group is responsible for the H-bonding.

b) For aspartate, the binding curve with serotine is not very much different from glutamate which indicates that aspartate has structural similiarity with glutamate. Aspartate also has a free carboxylate moity (COO-) attached to an alkyl chain.

c) As the binding curve with isoleucine differ far from that of glutamate or aspartate , so the structure of isoleucine is different from glutamate or aspartate. From the binding curve, we find that the affinity is lower for isoleucine. It is because the isoleucine does not contain a free carboxylate group that can form H -bonding with serotonine. In isoleucine the -COOH group exists as zwitter ionic form with the NH2 group present in the molecule.