HIV protease

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Structure of HIV-1 protease

Identifiers
EC number	3.4.23.16
CAS number	143701-96-2
Alt. names
IntEnz	IntEnz view
BRENDA	BRENDA entry
ExPASy	NiceZyme view
KEGG	KEGG entry
MetaCyc	metabolic pathway

HIV Protease is an essential enzyme in the life cycle of the Human Immunodeficiency Virus (HIV), the virus responsible for Acquired Immunodeficiency Syndrome (AIDS). It is a type of aspartic protease that cleaves newly synthesized polyproteins at specific sites to create the mature protein components of an infectious HIV virion.

Structure and Function

HIV protease is a homodimeric enzyme, meaning it consists of two identical subunits. Each subunit contributes an aspartic acid residue to the active site, which is crucial for the enzyme's catalytic activity. The active site of HIV protease is located in a cleft between the two subunits and is responsible for the hydrolysis of peptide bonds in the viral polyprotein precursors.

The enzyme recognizes and cleaves at specific sites within the Gag-Pol polyprotein, which is essential for the maturation of the virus. The cleavage of these polyproteins results in the formation of the structural proteins and enzymes necessary for the assembly of a mature and infectious HIV particle.

Role in HIV Life Cycle

HIV protease is critical in the late stages of the HIV life cycle. After the virus enters a host cell and reverse transcription occurs, the resulting DNA is integrated into the host genome. The host cell machinery then transcribes and translates the viral genes into polyproteins. HIV protease cleaves these polyproteins into functional proteins, including the reverse transcriptase, integrase, and structural proteins of the virus.

Without the activity of HIV protease, the virus would produce non-infectious particles, as the necessary proteins would not be properly processed and assembled.

Inhibition and Drug Development

HIV protease is a major target for antiretroviral drugs known as protease inhibitors. These drugs bind to the active site of the enzyme, preventing it from cleaving the polyproteins. This inhibition results in the production of immature, non-infectious viral particles.

Some of the first protease inhibitors developed include saquinavir, ritonavir, and indinavir. These drugs have significantly improved the treatment outcomes for individuals with HIV/AIDS when used in combination with other antiretroviral therapies.

Resistance

HIV can develop resistance to protease inhibitors through mutations in the protease gene. These mutations can alter the structure of the enzyme, reducing the binding affinity of the inhibitors. As a result, combination therapies are often used to reduce the likelihood of resistance development.

Research and Future Directions

Ongoing research aims to develop new protease inhibitors with improved efficacy and reduced side effects. Additionally, understanding the mechanisms of resistance can lead to the design of drugs that are less susceptible to resistance.

Also see

• HIV Life Cycle
• Antiretroviral Therapy
• Protease Inhibitors
• Reverse Transcriptase
• Integrase