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HIV-1 proteaseHIV-1 protease

HIV-1 Protease is a viral aspartic protease that responsible for maturation of human immunodeficiency virus (HIV).

HIV-1 protease cleaves an human immunodeficiency virus (HIV) precursor proteins, such as cleaving the env protein,glycoprotein (GP) 160, into gp41 and gp120. Gp120 protrudes from the surface of HIV and binds to CD4+ T cells and gp41 embedded in the outer envelope help gp120 bind CD4+ T cells, and they both play a role in HIV's infection of CD4+ T cells. Therefore, HIV-1 protease make the virus have the ability to infect new cells by the cleave process. In other words, HIV-1 protease is responsible for maturation of the virion by cleaving proteins into their mature form.

Because the cleave step results in infectious viral particles, Drugs called protease inhibitors can interfere with this step of the viral life cycle and further prevent HIV infection progressing. Thus, many drug designs or much pharmaceutical research conduct by understanding the structure of HIV-1 protease active site and by inhibition of its activity disrupts HIV’s ability to replicate and infect additional cells.

spinqualitylabelsall models PDB ID 1hsg Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image
1hsg, resolution 2.00Å ()
Ligands:
Gene:	HIV-1 PROTEASE FROM THE NY5 ISOLATE (Human immunodeficiency virus 1)
Structural annotation: Resources: CATH : 1Hsga00, 1Hsgb00 InterPro : Ipr010659, Ipr010999, Ipr001995, Ipr008916, Ipr010661, Ipr002156, Ipr001878, Ipr000071, Ipr000721, Ipr012337, Ipr001037, Ipr009007, Ipr001969, Ipr008919, Ipr003308, Ipr000477, Ipr013084, Ipr001584 Pfam : PF00077 SCOP : d1hsga_, d1hsgb_ UniProt : P03367
Functional annotation: Cellular component: cytoplasm viral nucleocapsid nucleus membrane viral capsid virion Biological process: viral reproduction viral procapsid maturation DNA integration proteolysis DNA recombination RNA-dependent DNA replication transposition, DNA-mediated Molecular function: hydrolase activity nucleotidyltransferase activity ribonuclease H activity nucleic acid binding aspartic-type endopeptidase activity peptidase activity endonuclease activity DNA binding transferase activity RNA-directed DNA polymerase activity metal ion binding structural molecule activity RNA binding magnesium ion binding DNA-directed DNA polymerase activity zinc ion binding nuclease activity catalytic activity integrase activity
Evolutionary conservation: Toggle Conservation Colors: Rows = identical sequences: Further Information: Caveats, Explanation, Complete Results at ConSurfDB
Resources:	FirstGlance, OCA, RCSB, PDBsum
Coordinates:	save as pdb, mmCIF, xml

BackgroundBackground

World wide, the predominant virus is HIV-1 – associated with high number of deaths.

As of January 2006, it has been estimated that AIDS has killed more than 25 million people since it was first recognized on December 1, 1981.

The new viral particles cannot enter the host cell without maturation which require HIV-encoded protease.

Since HIV-1 protease play a vital role for infection, it has been studied as a drug target.

HIV genome and proteseHIV genome and protese

HIV genome contains three main genes: gag, pol, and env.

• gag gene codes for structural proteins which forms the ‘body’ of the viral particle, among other proteins.
• Pol gene on the other hand codes for three essential enzymes which are Reverse Transcriptase (RT), Integrase (IN) and Protease (PR), among other proteins.
• env gene codes for viral envelop proteins.

HIV-1 Protease acts as ‘chemical scissors’ to cleave the polyproteins into functional constituent proteins. This maturation process occurs as the virion buds from the host cell.

The genome products (red circle) that require protease to process.

ReferenceReference

• Twenty years of therapy for HIV-1 infection, Roger J Pomerantz & David L Horn, Nature Medicine 9, 867-873, 2003

• Retroviral proteases, Ben M Dunn, Maureen M Goodenow, Alla Gustchina, and Alexander Wlodawer, Genome Biol. 2002; 3(4): reviews3006.1–reviews3006.7.

• Crystal Structures of Highly Constrained Substrate and Hydrolysis Products Bound to HIV-1 Protease. Implications for the Catalytic Mechanism, Joel D. A. Tyndall, Leonard K. Pattenden, Robert C. Reid, Shu-Hong Hu, Dianne Alewood, Paul F. Alewood, Terry Walsh, David P. Fairlie and Jennifer L. Martin, Biochemistry, 2008, 47 (12), pp 3736–3744

• Solution Structure of the Mature HIV-1 Protease Monomer: INSIGHT INTO THE TERTIARY FOLD AND STABILITY OF A PRECURSOR, Rieko Ishima, Dennis A. Torchia, Shannon M. Lynch, Angela M. Gronenborn, and John M. Louis, J. Biol. Chem., Vol. 278, Issue 44, 43311-43319, October 31, 2003

• HIV-1 protease: mechanism and drug discovery, Ashraf Brik and Chi-Huey Wong, Org. Biomol. Chem., 2003, 1, 5 – 14

http://www.niaid.nih.gov/factsheets/hivinf.htm

http://www.stanford.edu/group/virus/retro/2005gongishmail/HIV.html

http://en.wikipedia.org/wiki/HIV