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'''HIV-1 Protease''' is a viral aspartic protease that responsible for maturation of [http://en.wikipedia.org/wiki/HIV human immunodeficiency virus (HIV)]. | '''HIV-1 Protease''' is a viral aspartic protease that responsible for maturation of [http://en.wikipedia.org/wiki/HIV human immunodeficiency virus (HIV)]. | ||
HIV-1 protease cleaves an [http://en.wikipedia.org/wiki/HIV human immunodeficiency virus (HIV)] precursor proteins, such as cleaving the [http://en.wikipedia.org/wiki/HIV#Replication_cycle env protein],[http://en.wikipedia.org/wiki/Gp160 glycoprotein (GP) 160], into [http://en.wikipedia.org/wiki/Gp160#gp41 gp41] | HIV-1 protease cleaves an [http://en.wikipedia.org/wiki/HIV human immunodeficiency virus (HIV)] precursor proteins, such as cleaving the [http://en.wikipedia.org/wiki/HIV#Replication_cycle env protein], [http://en.wikipedia.org/wiki/Gp160 glycoprotein (GP) 160], into [http://en.wikipedia.org/wiki/Gp160#gp41 gp41] | ||
and [http://en.wikipedia.org/wiki/Gp160#gp120 gp120]. [http://en.wikipedia.org/wiki/Gp160#gp120 Gp120] protrudes from the surface of HIV and binds to CD4+ T cells and [http://en.wikipedia.org/wiki/Gp160#gp41 gp41] | and [http://en.wikipedia.org/wiki/Gp160#gp120 gp120]. [http://en.wikipedia.org/wiki/Gp160#gp120 Gp120] protrudes from the surface of HIV and binds to CD4+ T cells and [http://en.wikipedia.org/wiki/Gp160#gp41 gp41] | ||
embedded in the outer envelope help [http://en.wikipedia.org/wiki/Gp160#gp120 gp120] bind CD4+ T cells, and they both play a role in HIV's infection of [http://en.wikipedia.org/wiki/CD4_cell 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 [http://en.wikipedia.org/wiki/Virion virion] by cleaving proteins into their mature form. | embedded in the outer envelope help [http://en.wikipedia.org/wiki/Gp160#gp120 gp120] bind CD4+ T cells, and they both play a role in HIV's infection of [http://en.wikipedia.org/wiki/CD4_cell 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 [http://en.wikipedia.org/wiki/Virion virion] by cleaving proteins into their mature form. | ||
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[[Image:Infection_process.jpg|350px]] | [[Image:Infection_process.jpg|350px]] | ||
== HIV genome and protease == | == HIV genome and HIV-1 protease == | ||
HIV genome contains three main genes: gag, pol, and env. | HIV genome contains three main genes: gag, pol, and env. | ||
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*This domain is quite useful in dimer stabilization, as well as the catalytic site stability. | *This domain is quite useful in dimer stabilization, as well as the catalytic site stability. | ||
*The interface between the core and terminal domains is composed primarily of small hydrophobic residues. The helix of the terminal domain packs against several beta-strands of the core domain. | *The interface between the core and terminal domains is composed primarily of small hydrophobic residues. The helix of the terminal domain packs against several beta-strands of the core domain. | ||
[[Image:Domains.png|550px]] | |||
''The flap domains'' | ''The flap domains'' | ||
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*Flexible flaps enclose the active site and provide important ligand binding interactions. | *Flexible flaps enclose the active site and provide important ligand binding interactions. | ||
[[Image: | [[Image:Binding and catalytic site.jpg|550px]] | ||
== Structure analysis == | |||
The concavity analysis shown below can be used to determine possible binding spots. The most likely spot shown red determined with [http://hotpatch.mbi.ucla.edu/ HotPatch] | |||
[[Image:Concavity.png|460px]] | |||
Conserved residues for this protein was analyzed with [http://consurf.tau.ac.il/index.html ConSurf] | |||
[[Image:ConSurf outptus.jpg|460px]] | |||
== Reference == | == Reference == | ||
*Twenty years of therapy for HIV-1 infection | *<ref name= "{history}"> Roger J Pomerantz & David L Horn, Twenty years of therapy for HIV-1 infection, Nature Medicine, 2003, 9, 867-873, </ref> | ||
<references/> | |||
*Retroviral proteases, Ben M Dunn, Maureen M Goodenow, Alla Gustchina, and Alexander Wlodawer, Genome Biol. 2002; 3(4): reviews3006.1–reviews3006.7. | *Retroviral proteases, Ben M Dunn, Maureen M Goodenow, Alla Gustchina, and Alexander Wlodawer, Genome Biol. 2002; 3(4): reviews3006.1–reviews3006.7. | ||