HIV-1 protease
HIV-1 Protease (Retropepsin) | |||||||||
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ExPASy NiceZyme view | | ||||||||
KEGG | KEGG entry | ||||||||
MetaCyc | metabolic pathway | ||||||||
PRIAM | profile | ||||||||
PDB structures | RCSB PDB PDBe PDBsum | ||||||||
Gene Ontology | AmiGO / QuickGO | ||||||||
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HIV-1 protease or PR is a
Structure
Mature HIV protease exists as a 22 kDa
Biosynthesis
Precursor
The Gag-Pol polyprotein, which contains premature coding proteins, including HIV-1 PR.[9] PR is located between the reverse transcriptase (which is at the C-terminus of PR) and the p6pol (which is at the N-terminus of PR) of the transframe region (TFR).[11]
In order for this precursor to become a functional protein, each monomer must associate with another HIV-1 PR monomer to form a functional catalytic active site by each contributing the Asp25 of their respective catalytic triads.[9]
Synthesis Mechanism
When viral HIV-RNA enters the cell, it is accompanied by a reverse transcriptase, an integrase, and a mature HIV-1 PR. The reverse transcriptase converts viral RNA into DNA, facilitating the integrase's role in incorporating viral genetic information with the host cell DNA.[2] The viral DNA can either remain dormant in the nucleus or be transcribed into mRNA and translated by the host cell into the Gag-Pol polyprotein, which would then be cleaved into individual functional proteins (including a newly synthesized HIV-1 PR) by the mature HIV-1 PR.[9]
The HIV-1 PR precursor catalyzes its own production by facilitating its cleavage from the Gag-Pol polyprotein in a mechanism known as auto-processing. Auto-processing of HIV-1 PR is characterized by two sequential steps: (1) the intramolecular cleavage of the N-terminus at the p6pol-protease cleavage site, which serves to finalize PR processing and increase enzymatic activity with the newly formed PR-reverse transcriptase intermediate, and (2) the intermolecular cleavage of the C-terminus at the protease-reverse transcriptase cleavage site, leading to the assembly of two PR subunits into mature dimers.