The following covalent inhibitor blocks function in a protease found in the porcine epidemic diarrhea virus by reacting with a cysteine amino acid residue (shown below) in the active site. Draw the expected complex that forms between the inhibitor and the enzyme active site (J. Med. Chem. 2017, 60, 3212–3216.) [Assume the presence of active site bases if you need them.]
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Verified step by step guidance

1. Identify the functional groups present in the inhibitor molecule that can react with the cysteine residue in the enzyme's active site. Typically, look for electrophilic centers such as carbonyl groups or Michael acceptors.
2. Recognize the nucleophilic nature of the cysteine residue, which contains a thiol group (-SH). The sulfur atom in the thiol group is a good nucleophile and can attack electrophilic centers.
3. Consider the mechanism of covalent inhibition, where the thiol group of cysteine attacks the electrophilic center of the inhibitor, forming a covalent bond. This often involves a nucleophilic addition or substitution reaction.
4. Assume the presence of active site bases that can facilitate the reaction by deprotonating the thiol group, enhancing its nucleophilicity. This step is crucial for the formation of the covalent bond.
5. Draw the resulting complex, showing the covalent bond formed between the sulfur atom of the cysteine residue and the electrophilic center of the inhibitor. Ensure to depict any changes in the inhibitor's structure due to the reaction.

Key Concepts

Covalent Inhibition

Covalent inhibition involves the formation of a covalent bond between an inhibitor and a target enzyme, leading to irreversible enzyme inactivation. This type of inhibition is particularly effective because it permanently alters the enzyme's active site, preventing substrate binding and subsequent catalytic activity. Understanding the mechanism of covalent inhibition is crucial for designing inhibitors that can effectively block enzyme function.

Active Site Chemistry

The active site of an enzyme is the region where substrate molecules bind and undergo a chemical reaction. It often contains amino acid residues that facilitate catalysis, such as cysteine, which can form covalent bonds with inhibitors. Knowledge of active site chemistry, including the role of specific residues and potential interactions, is essential for predicting how inhibitors will bind and modify enzyme activity.

Role of Cysteine in Enzyme Function

Cysteine is an amino acid that plays a critical role in enzyme function due to its thiol group, which can participate in nucleophilic reactions. In the context of proteases, cysteine residues are often involved in catalysis and can be targeted by covalent inhibitors. Understanding cysteine's reactivity and its position within the active site is vital for designing inhibitors that can effectively block enzyme activity by forming covalent bonds.