User:Tsung-Yi Lin/Sandbox: Difference between revisions

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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 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]

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

[[Image:Infection_process.jpg|350px]]

== HIV genome and HIV-1 protease ==

== HIV 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.

* 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.

[[Image:Genome_and_protease.jpg|center|350px|thumb|The genome products (red circle) that require protease to process.]]

== HIV-1 protease structure ==

'''Family and Biological unit'''

*HIV-1 protease belongs to aspartic family, which also includes digestive enzyme pepsin, the lysosomal cathepsin, share common catalytic mechanism

*It functions as a homodimer (two identical polypeptide chains) with only one active site.

*It consists 99 amino acids, which forming 10 β-strand and 1 α-helix.

[[Image:Mechanism.jpg|650px]]

'''Domains in HIV-1 protease'''

''Terminal domain or dimerization domain''

*Consists of the termini four-stranded beta-sheet; (residues 1-4, and 95-99 of each monomer), the turn encompassing residues 4-9, and the helix (residues 86-94 of each monomer). This domain is quite crucial in dimer formation and stabilization of an active PR.

''The core domains''

*These are two; one from each monomer.

*Composed of primarily four beta-strand structures; and is quite compact.

*Residues 10-32 and 63-85 from each monomer make up the domain sequence

*The conserved Asp25-Thr26-Gly27 catalytic triad, is situated at the interface of the core domains from the two monomers.

*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.

[[Image:Domains.png|550px]]

''The flap domains''

*This domain includes a mostly solvent exposed loop (residue 33-43) preceding the beta hairpin containing the flaps (residue 44-63).

*Flexible flaps enclose the active site and provide important ligand binding interactions.

[[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 ==

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

*<ref name= "{history}"> Roger J Pomerantz & David L Horn, Twenty years of therapy for HIV-1 infection, Nature Medicine, 2003, 9, 867-873, </ref>

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

@@ Line 3: / Line 3: @@
 '''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]
 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.
@@ Line 20: / Line 20: @@
 Since HIV-1 protease play a vital role for infection, it has been studied as a drug target.
+[[Image:Infection_process.jpg|350px]]
+== HIV genome and HIV-1 protease ==
-== HIV 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.
+* 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.
+[[Image:Genome_and_protease.jpg|center|350px|thumb|The genome products (red circle) that require protease to process.]]
+== HIV-1 protease structure ==
+'''Family and Biological unit'''
+*HIV-1 protease belongs to aspartic family, which also includes digestive enzyme pepsin, the lysosomal cathepsin, share common catalytic mechanism
+*It functions as a homodimer (two identical polypeptide chains) with only one active site.
+*It consists 99 amino acids, which forming 10 β-strand and 1 α-helix.
+[[Image:Mechanism.jpg|650px]]
+'''Domains in HIV-1 protease'''
+''Terminal domain or dimerization domain''
+*Consists of the termini four-stranded beta-sheet; (residues 1-4, and 95-99 of each monomer), the turn encompassing residues 4-9, and the helix (residues 86-94 of each monomer). This domain is quite crucial in dimer formation and stabilization of an active PR.
+''The core domains''
+*These are two; one from each monomer.
+*Composed of primarily four beta-strand structures; and is quite compact.
+*Residues 10-32 and 63-85 from each monomer make up the domain sequence
+*The conserved Asp25-Thr26-Gly27 catalytic triad, is situated at the interface of the core domains from the two monomers.
+*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.
+[[Image:Domains.png|550px]]
+''The flap domains''
+*This domain includes a mostly solvent exposed loop (residue 33-43) preceding the beta hairpin containing the flaps (residue 44-63).
+*Flexible flaps enclose the active site and provide important ligand binding interactions.
+[[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 ==
-*Twenty years of therapy for HIV-1 infection, Roger J Pomerantz & David L Horn, Nature Medicine 9, 867-873, 2003
+*<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.