Are competitive/uncompetitive/noncompetitive/mixed inhibitors known? Are these inhibitors reversible or irreversible? Are any clinically used/applicable/sold as drugs?Explain

Description

Answer the following questions (1 page per question minimum). Use external resources (all sources needed have been provided) as the data needed to write this paper.

1. Secondary/tertiary/quaternary structure if known, otherwise any efforts to obtain the structure and/or why is doing so a problem?

2. Important amino acid residues for binding (if receptor/enzyme) and for catalysis (if enzyme)

3. Types of interactions important in binding (hydrogen bonds, electrostatics, van der Waals, etc.)

4. Enzyme catalysis: Necessary cofactors, proposed catalytic mechanism, important catalytic principles (metals, general acid/base, nucleophilic or electrophilic chemistry)

5. Function/reaction, kinetics and/or binding affinity as applicable. (For non-enzyme proteins, kinetics will almost certainly NOT apply…but binding of ligand should be discussed in some way.) Kinetics include: Michaelis-Menten/steady-state parameters (kcat, Km), are there multiple substrates? Is sequential vs. ping-pong and/or random vs. ordered known? For binding affinity for a non-enzyme protein, is Kd (dissociation constant) known? Do multiple compounds bind, presumably with different binding affinities? What is/are the “best” substrates/ligands for binding?

6. Inhibitors: Are competitive/uncompetitive/noncompetitive/mixed inhibitors known? Are these inhibitors reversible or irreversible? Are any clinically used/applicable/sold as drugs?

7. pH dependence: Is anything known about the pH dependence of your protein/enzyme of interest? This part of your paper should focus on pH changing the activity and/or binding of your enzyme/protein and should NOT focus on “stability” or denaturation. If you chose a non-enzyme protein, it is much less likely you will have much to say about this. You may be able to make some general conclusions/hypotheses, though. For instance, if it turns out that an aspartate residue is critical for ligand binding, a significant change in pH would be likely to disrupt that interaction. If the binding interactions are mostly hydrophobic/van der Waals, pH is much less likely to have an effect.

 

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