Function of HIV Protease

  • The first viral enzyme encoded by the pol gene is protease. [1].

  • During viral maturation, protease cleaves Gag polyproteins at the cleavage sites to produce structural proteins (Matrix, Capsid, Nucleocapsid, p6). Protease cleaves the GagPol polyproteins to produce viral enzymes (Protease, Reverse transcriptase, Integrase). .

  • The activity of protease depends on the concentration of GagPol polyproteins and the rate of protease-mediated autoprocessing is modulated by the adjacent p6 sequence [1].

Reference

  1. Zybarth G, Carter C: Domains upstream of the protease (PR) in human immunodeficiency virus type 1 Gag-Pol influence PR autoprocessing. J Virol 1995, 69:3878-3884.(Download Article)

Sequence

(1) Reference sequence for HIV-1 Protease

  • Strain: HIV-1 subtype B HXB2 (ID: K03455)

  • Fasta format: Download

  • Reference sequence: 

  1       10         20         30         40         50
  |        |          |          |          |          | 
  PQVTLWQRPL VTIKIGGQLK EALLDTGADD TVLEEMSLPG RWKPKMIGGI 
  51      60         70         80         90        99
  |        |          |          |          |         | 
  GGFIKVRQYD QILIEICGHK AIGTVLVGPT PVNIIGRNLL TQIGCTLNF

(2) Reference sequence for HIV-2 and SIV Protease

  • Strain: SIV Mac239 (ID: M33262)

  • Fasta format: Download

  • Reference sequence: 

  1       10         20         30         40         50
  |        |          |          |          |          | 
  PQFSLWRRPV VTAHIEGQPV EVLLDTGADD SIVTGIELGP HYTPKIVGGI 
  51      60         70         80         90        99
  |        |          |          |          |         | 
  GGFINTKEYK NVEIEVLGKR IKGTIMTGDT PINIFGRNLL TALGMSLNF

(3) Coloring scheme for above amino acids

  1. Amino acids with hydrophobic side chains (normally buried inside the protein core):

    • A - Ala - Alanine

    • I - Ile - Isoleucine

    • L - Leu - Leucine

    • M - Met - Methionine

    • V - Val - Valine

  2. Amino acids with polar uncharged side chains (may participate in hydrogen bonds):

    • N - Asn - Asparagine

    • Q - Gln - Glutamine

    • S - Ser - Serine

    • T - Thr - Threonine

  3. Amino acids with positive charged side chains:

    • H - His - Histidine

    • K - Lys - Lysine

    • R - Arg - Arginine

  4. Amino acids with negative charged side chains:

    • D - Asp - Aspartic acid

    • E - Glu - Glutamic acid

  5. Amino acids with aromatic side chains:

    • F - Phe - Phenylalanine

    • Y - Tyr - Tyrosine

    • W - Trp - Tryptophan

  6. Cysteine: C - Cys - Cysteine

  7. Glycine: G - Gly - Glycine

  8. Proline: P - Pro - Proline

Amino acid variations at HIV-1 Protease

Here, we visualize the prevalence of amino acid variations at the HIV-1 Protease from HIV-1 subtype B.

Protocal of our sequence collection

  • For HIV-1 subtype B, one sequence per patient was extracted from HIV Los Alamos database (www.hiv.lanl.gov/).

  • We removed misclassified sequences or sequences with hypermutations, stop codons, ambiguous nucleotides, which were described in our article [1].

  • We removed sequences conferred partial or full resistance to any of the protease inhibitors, RT inhibitors and integrase inhibitors using HIVdb V6.0 .

Visualization

Our sequence dataset of HIV-1 subtype B Protease included 4725 sequences. In the following picture, HXB2 indices of individual proteins are shown on top of the colored bars. A consensus amino acid at each position is shown beneath the colored bar. Natural variations are shown below the consensus amino acids; proportions (%) are colored red if they were more than 5%; blue otherwise.


HIV-1 protein interaction patterns.

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Please cite our article:

  1. Guangdi Li, Supinya Piampongsant, Nuno Rodrigues Faria, Arnout Voet, Andrea-Clemencia Pineda-Peña, Ricardo Khouri, Philippe Lemey, Anne-Mieke Vandamme, Kristof Theys. An integrated map of HIV genome-wide variation from a population perspective. Retrovirology 12, 18, doi:10.1186/s12977-015-0148-6 (2015). [PDF] [PubMed Link]

Structure

(1) Secondary structure of HIV-1 Protease

Here, we visualize the secondary structure of HIV-1 Protease using PDBSum (PDB code: 1A30)



(2) Tertiary structure of HIV-1 Protease

Here, we provide a structure movie of Protease using PyMOL V1.7 (PDB code: 1A30). Alpha-helix and beta-strand secondary structures are demonstrated by red .

Localization

(1) Coding region of Protease at the HIV genome


(2) Localization of Protease during the HIV-1 life cycle

Here, we visualize the localization of Protease during the viral life cycle. Red stars indicate the appearance of HIV-1 Protease.


Anti-HIV inhibitor

(1) Drug binding pocket of HIV-1 Protease

Here, we visualize the drug binding pocket of HIV-1 Protease



(2) List of known inhibitors targeting HIV-1 Protease

Here, we summarize the published anti-HIV inhibitors which bind to HIV-1 Protease.



Protein-protein interactions