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Questions and Answers
What is the primary role of the HIV protease enzyme?
What is the primary role of the HIV protease enzyme?
What structural feature is critical for the binding of HIV protease inhibitors?
What structural feature is critical for the binding of HIV protease inhibitors?
Which mechanism does the HIV protease utilize to catalyze the cleavage of peptide bonds?
Which mechanism does the HIV protease utilize to catalyze the cleavage of peptide bonds?
What do the aromatic groups in the HIV protease inhibitors primarily target?
What do the aromatic groups in the HIV protease inhibitors primarily target?
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How do HIV protease inhibitors mimic the tetrahedral intermediate during catalysis?
How do HIV protease inhibitors mimic the tetrahedral intermediate during catalysis?
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Which type of amino acids have non-polar, aliphatic R groups?
Which type of amino acids have non-polar, aliphatic R groups?
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What is a key factor determining the function of a protein?
What is a key factor determining the function of a protein?
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Which protein structure is characterized by the association of multiple polypeptide chains?
Which protein structure is characterized by the association of multiple polypeptide chains?
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Which of the following proteins is primarily involved in oxygen transport in muscle?
Which of the following proteins is primarily involved in oxygen transport in muscle?
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What structural role do proteins play related to bone and connective tissue?
What structural role do proteins play related to bone and connective tissue?
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Study Notes
HIV Protease
- Cleaves peptide bonds between phenylalanine (Phe) and proline (Pro) residues in polyproteins
- Active site contains a pocket for binding aromatic groups
Mechanism of Action
- Uses general base catalysis involving water to attack the carbonyl carbon
- Forms a tetrahedral intermediate
- Releases the amino acid leaving group while protonating it
HIV Protease Inhibitors
- Structurally diverse but share a common core structure: a main chain with a hydroxyl group next to a benzyl group side chain
- Target the aromatic binding pocket with the benzyl group
- Designed based on the transition-state analog
- The adjacent hydroxyl group mimics the negatively charged oxygen atom of the tetrahedral intermediate
- The remaining parts of the inhibitors fit into specific crevices on the enzyme surface to enhance binding
Protein Structure
- Proteins are made up of 20 different amino acids, each with a unique side chain ("R group") that gives it specific properties.
- Amino acids are zwitterions, meaning they have both a positive and negative charge at physiological pH.
- The amino acid sequence of a protein is called its primary structure.
- The three-dimensional structure of a protein is determined by its primary structure and is critical for its function.
- Secondary structure refers to local folding patterns within the protein, such as alpha-helices and beta-sheets.
- Tertiary structure describes the overall 3D shape of a single protein chain.
- Quaternary structure describes the arrangement of multiple protein subunits in a complex.
- The peptide bond forms between the carboxyl group of one amino acid and the amino group of another, resulting in a planar peptide group.
- Sickle-cell anemia is a disease caused by a single amino acid mutation in the beta-globin subunit of hemoglobin.
Protein Function
- Proteins perform a wide range of functions in the body, including structural support, catalysis, transport, metabolic control, and contraction.
- Enzyme proteins catalyze metabolic reactions.
- DNA-binding proteins regulate gene expression.
- Hemoglobin and myoglobin transport oxygen.
- Immunoglobulins and interferon protect against infection.
- Fibrin helps to stop bleeding.
Denaturation and Folding
- Denaturation is the process of unfolding a protein, often caused by heat, pH changes, or chemicals.
- Protein folding is the process by which a protein takes on its correct 3D structure.
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Description
This quiz explores the mechanisms of action of HIV protease, including its active site interactions and catalytic process. Additionally, it examines the structural characteristics of HIV protease inhibitors and their design principles. Test your knowledge on the critical aspects of HIV treatment and enzyme inhibition.