Question

Triosephosphate isomerase (pdb code 1TPH) has a glutamate (residue 165) in the active site that abstracts a proton from the substrate dihydroxyacetone phosphate forming an enolate intermediate. Use your favorite molecular modeling program (PYMOL probably) and explore the environment of the active site glutamate. Would you expect the pKa of glutamate 165 to be higher than normal? If so, explain why using logic related to stabilization of one side or the other of the proton equilibrium

Answer 1

Yes, we expect the pKa of glutamate to be higher than normal

Step-by-step explanation:

Data Given:

Triosephosphate isomerase (pdb code 1TPH) has a glutamate (residue 165)

Data Analysis:

Located in the active sites, we can define active sites as regional sites where enzymatic activities takes place. In the given question regarding the active sites of the glutamate , substrates binds at these molecules bind sites and undergo chemical reactions.

However , the key enzyme glutamate dehydrogenase contains two domains which are partitioned by a cleft located in the site. Of which one domain actively engages in nucleotide binding and the substrate.We infer the process to be catalytic and during the process of this catalytic cycle, movements of these molecules occurs.

Now; in the region of the glutamate active sites, The interaction between the gamma-carbonyl group is brought by the a two-residue factor making interactions of the glutamate substrate. Hence, glutamate 165 have the tendency of behaving as a donating acid which we expect the pKa value to be 6.4 which is higher than normal.

Conclusion: Weak acids have low energies as strong acids have higher energies and which the reaction favors the lower side in the proton equilibrium.

Answer 2

In the active sites of the enzymes, many molecules of the substrate bind and cause a chemical reaction, with respect to the active site in glutamate, we know that the enzyme glutamate dehydrogenase has two separate domains with a cleft in which the active site is located, one of the domains causes the binding of dinucleotide and the other carries with it the majority of the residues that bind to the substrate, thus when Contact occurs, at the active site two residues interact with the gamma-carboxyl group of the glutamate substrate.

About Glutomate 165 it is capable of acting as a donor acid and has a pKa value of 6.4, which is higher than normal. Weak acids have low energies compared to strong acids and the reaction favors the lower energy side of the proton balance.