What is the structure of HIV protease?
Mature HIV protease exists as a 22 kDa homodimer, with each subunit made up of 99 amino acids. A single active site lies between the identical subunits and has the characteristic Asp-Thr-Gly (Asp25, Thr26 and Gly27) catalytic triad sequence common to aspartic proteases.
How many protein units make up the HIV protease enzyme?
two
HIV-1 protease is a small enzyme, composed of two identical protein chains, each only 99 amino acids long.
Where does HIV protease cleave?
HIV protease is an aspartyl proteinase responsible for cleaving the Gag and Gag-Pol polyproteins in a late stage of the viral life cycle. Because there is no corresponding aspartyl protease that cleaves the Gag polyprotein in mammalian cells, HIV protease has been a popular target for antiretroviral drug development.
What are the accessory proteins of HIV?
The Human Immunodeficiency Virus (HIV) genome encodes three major structural proteins common to all retroviruses (Gag, Pol and Env), two regulatory proteins (Tat and Rev) that are essential for viral replication, and four accessory proteins (Nef, Vif, Vpu, Vpr).
What do viral proteases do?
Viral proteases are enzymes (endopeptidases EC 3.4. 2) encoded by the genetic material (DNA or RNA) of viral pathogens. The role of these enzymes is to catalyze the cleavage of specific peptide bonds in viral polyprotein precursors or in cellular proteins.
How does a protease inhibitor work?
Protease inhibitors, which figure among the key drugs used to treat HIV, work by binding to proteolytic enzymes (proteases). That blocks their ability to function. Protease inhibitors don’t cure HIV. But by blocking proteases, they can stop HIV from reproducing itself.
Do all viruses have proteases?
Not all viruses encode a protease (PR), but those that do ensure that proteolytic action occurs at the proper time and place, independent of the host for this essential function. In general, these viruses express polyproteins that are precisely cleaved by the viral protease(s) during replication and particle assembly.
What is the action of protease?
Protease refers to a group of enzymes whose catalytic function is to hydrolyze peptide bonds of proteins. They are also called proteolytic enzymes or proteinases. For example, in the small intestine, proteases digest dietary proteins to allow absorption of amino acids.
What stage do Protease inhibitors prevent?
Protease inhibitors prevent viral replication by selectively binding to viral proteases (e.g. HIV-1 protease) and blocking proteolytic cleavage of protein precursors that are necessary for the production of infectious viral particles.
How long have protease inhibitors been around?
The first protease inhibitor to be approved by the US Food and Drug Administration (FDA) was saquinavir, in December 1995, a mere 97 days after the FDA received its marketing application. Within months, two other protease inhibitors, ritonavir and indinavir, were also approved.
How many amino acids are in HIV protease?
Mature HIV protease exists as a 22kDa homodimer, with each subunit made up of 99 amino acids. A single active site lies between the identical subunits and has the characteristic Asp-Thr-Gly (Asp25, Thr26 and Gly27) catalytic triad sequence common to aspartic proteases.
What does HIV-1 protease dimer look like?
HIV-1 protease dimer in white and grey, with peptide substrate in black and active site aspartate side chains in red. (PDB: 1KJF)
What are the S1 and S3 subsites of HIV protease?
The S3 subsites are adjacent to S1 subsites and are also mostly hydrophobic. 3.3 Mechanism of the HIV protease. Proteases are known to play essential roles in many biological processes. They catalyze the hydrolysis of peptide bonds with high sequence selectivity and catalytic proficiency.
Where is HIV protease located in the body?
These amino acids are located at position 25, 26, and 27, and are responsible for the catalytic activity. With its integral role in HIV replication, HIV protease has been a prime target for drug therapy.