Biochemistry Homework

Question

Which of the following is responsible for nucleophilic attack on the substrate during the reaction catalyzed by Trypsin?

	The positively charged side chain of Histidine.
	The negatively charged side chain of aspartate.
	The negatively charged side chain of Serine.
	The H of Glycine.

Answer 1

The negatively charged side chain of serine.

We can eliminate Glycine and histidine based on the definition of a nucleophile as this is a molecule that is electron-rich. Hydrogens typically don't fall in this category and positive side chains definitely don't.

Now that we have narrowed it down, it is important to understand the structure of trypsin to properly answer this question. Serine and Aspartate are both present in its catalytic site but only Serine is directly involved in the reaction as a result of proton loss which causes it to become negative. Aspartate is simply there for stability and is just along for the ride.