File:C-ter domain.jpg

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=='''3lpt - HIV integrase'''==

<StructureSection load='3lpt' size='340' side='right' caption='[[3lpt]], [[Resolution|resolution]] 2.00Å' scene=''>
3lt is an integrase of the HIV, the Human Immunodeficiency Virus. An integrase is an enzyme produced by a retrovirus to integrate its genetic material into the DNA of the infected cell. It is one of three enzymes of HIV, the others being the Reverse Transcriptase and the Protease.

== Structural highlights ==

<scene name='80/802676/Hiv_integrase_3lpt/8'>HIV Integrase 3D structure</scene>

<table><tr><td colspan='2'>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=723:(6-CHLORO-2-OXO-4-PHENYL-1,2-DIHYDROQUINOLIN-3-YL)ACETIC+ACID'>723</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=P03:2-[3-[3-(2-HYDROXYETHOXY)PROPOXY]PROPOXY]ETHANOL'>P03</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CAF:S-DIMETHYLARSINOYL-CYSTEINE'>CAF</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1hyv|1hyv]], [[3lpu|3lpu]]</td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3lpt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3lpt OCA], [http://pdbe.org/3lpt PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3lpt RCSB], [http://www.ebi.ac.uk/pdbsum/3lpt PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3lpt ProSAT]</span></td></tr>
</table>

== Function ==

HIV integrase is an enzyme required for the integration of viral DNA into the host genome. The process of integration can be divided into two sequential reactions. In the first one, named 3'-processing, the enzyme removes di- or trinucleotides from viral DNA ends to expose 3′-hydroxyls attached to the invariant CA dinucleotides. The second step is the insertion of the processed 3′-viral DNA ends into the host chromosomal DNA by a trans-esterification reaction. This is the strand transfer.

== Interaction with LEDGF/p75 and antiviral ==

Research on HIV show that the integrase use a protein, the LEDGF/p75 cofactor, so as to the preintegration complex is ligated to the DNA.
Some recents experimental antiviral inhibe this interaction and unable the integrase to interact with the cofactor. Thus, the DNA wouldn’t be inserted into the genome of the cell.

== Structure ==

HIV-1 integrase is composed of three domains: the N-terminal (residues 1-49), the core domain (residues 50-212) and the C-terminal domain (residues 213-288). The core domain is responsible for the catalytic activity of the enzyme. It contains three acidic residues, the D,D-35-E motif which plays a key role in catalysis. The N-terminal domain includes the conserved HHCC motif, which binds zinc. The C-terminal domain is less well conserved. [http://www.jbc.org/content/276/26/23213/F2.expansion.html]

====Structure and role of the core domain in the integration====

'''The three domain of the HIV integrase:'''

[[Image:Domain_HIV_Integrase.jpg]]

'''HIV Integrase sequence:'''

[[Image:HIV integrase sequenc.jpg]][https://www.uniprot.org/uniprot/Q76353#sequences] Length:288, Mass (Da):32,199

[[Image:HIV Integrase sequence.jpg]]

====Structure and role of the core domain====

The catalytic core domain contains three acidic residues, the D,D-35-E motif, comprising residues Asp64, Asp116, and Glu152. By analogy with models of catalysis by DNA polymerases, it has been proposed that coordination of divalent metal ion to these residues plays a key role in catalysis. The catalytic residues Asp64, Asp116, and Glu152of HIV-1 integrase and their counterparts in the ASV structures are in close proximity, coordinate divalent metal ion, and define the active site. However, the residues comprising the active site region exhibit considerable flexibility, suggesting that binding of DNA substrate is required to impose the precise configuration of residues that are required for catalysis.

[[Image:Core enzyme.jpg]]

====Structure and role of the N ter domain====

The N-terminal domain of HIV-1 integrase contains a conserved pair of His and Cys residues, a motif similar to the zinc-coordinating residues of zinc fingers. This domain binds zinc but its structure is totally different from that of zinc fingers. It consists of a bundle of three α-helices. It has an SH3 fold, although there is no known functional relationship with the SH3 domains of other proteins.

[[Image:Nter-domain.jpg]]

<scene name='80/802676/N-ter_domain/2'>Here is the 3D structure of the N-ter domain of the HIV integrase</scene>
<table><tr><td colspan='2'></td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
</table>

====Structure and role of the C ter domain====

[[Image:C-ter domain.jpg]]

====Structure and interaction with the antiviral====

The new experimental antirviral, here the (6-chloro-2-oxo-4-phenyl-1,2-dihydroquinolin-3-yl)acetic acid, interacts with the site with which <scene name='80/802676/Site_of_interaction/7'>the cofactor bind with the LEDGF/p75 cofactor</scene>. This site is situated in the core domain.
The molecule then inhibits the interaction between the LEDGF/p75 cofactor and the integrase.
The whole complex between the integrase and the cofactor is displayed on the proteopedia page [[2b4j]].

== HIV ==

HIV stands for human immunodeficiency virus. It is a retrovirus virus that damages the cells in the immune system and weakens the ability to fight everyday infections and disease. Copied into DNA, HIV is inserted into the genome of the infected cell thanks to integrases. To replicate and diffuse himself it attacks the body’s immune system, specifically the CD4 cells (T cells), which help fight off infections. As soon as HIV enters an individual, it accumulates in these cells and forms reservoirs of latent viruses in a few days or even hours. These reservoirs persist for life.

No cure currently exists, but HIV can be controlled by using antiretroviral therapy or ART. It is a combination of antiretroviral drugs to maximally suppress the HIV virus and stop the progression of HIV disease. Before the introduction of ART in the mid-1990s, people with HIV could progress to AIDS in just a few years. Today, someone diagnosed with HIV and treated before the disease is far advanced can live nearly as long as someone who does not have HIV.[https://www.hiv.gov/hiv-basics/overview/about-hiv-and-aids/what-are-hiv-and-aids]

== Disease: AIDS ==

AIDS is the ultimate stage of infection with the human immunodeficiency virus. The word AIDS stands for for Acquired Immunodeficiency Syndrome. People with AIDS get an increasing number of severe illnesses, called opportunistic infections, because of there damaged immune system. You are considered to have progressed to AIDS when the number of your CD4 cells falls below 200 cells per cubic millimeter of blood (200 cells/mm3). (In someone with a healthy immune system, CD4 counts are between 500 and 1,600 cells/mm3.) You are also considered to have progressed to AIDS if you develop one or more opportunistic illnesses, regardless of your CD4 count.[https://www.hiv.gov/hiv-basics/overview/about-hiv-and-aids/what-are-hiv-and-aids]

==See also==
http://proteopedia.org/wiki/index.php/2b4j :integrase ligated with the cofactor LEDGF/p75

== References ==
https://www.hiv.gov/hiv-basics/overview/about-hiv-and-aids/what-are-hiv-and-aids
https://www-nature-com.scd-rproxy.u-strasbg.fr/articles/nchembio.370
https://www.uniprot.org/uniprot/Q76353#sequences
http://pfam.xfam.org/family/rve
http://pfam.xfam.org/protein/Q76353_9HIV1
https://www.rcsb.org/3d-view/3LPT/1
https://en.wikipedia.org/wiki/Diethylene_glycol
https://microbewiki.kenyon.edu/index.php/HIV-1_Pre-Integration_Complex
https://www.uniprot.org/uniprot/Q76353
https://www.rcsb.org/structure/3lpt
http://proteopedia.org/wiki/index.php/Retroviral_Integrase
<references/>

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<scene name='80/802676/Site_of_interaction/1'>Text To Be Displayed</scene>{{Sandbox_Reserved_ESBS}}
=='''3lpt - HIV integrase'''==

<StructureSection load='3lpt' size='340' side='right' caption='[[3lpt]], [[Resolution|resolution]] 2.00Å' scene=''>
3lt is an integrase of the HIV, the Human Immunodeficiency Virus. An integrase is an enzyme produced by a retrovirus to integrate its genetic material into the DNA of the infected cell. It is one of three enzymes of HIV, the others being the Reverse Transcriptase and the Protease.

== Structural highlights ==
<table><tr><td colspan='2'>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=723:(6-CHLORO-2-OXO-4-PHENYL-1,2-DIHYDROQUINOLIN-3-YL)ACETIC+ACID'>723</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=P03:2-[3-[3-(2-HYDROXYETHOXY)PROPOXY]PROPOXY]ETHANOL'>P03</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CAF:S-DIMETHYLARSINOYL-CYSTEINE'>CAF</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1hyv|1hyv]], [[3lpu|3lpu]]</td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3lpt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3lpt OCA], [http://pdbe.org/3lpt PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3lpt RCSB], [http://www.ebi.ac.uk/pdbsum/3lpt PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3lpt ProSAT]</span></td></tr>
</table>

== Function ==

HIV integrase is an enzyme required for the integration of viral DNA into the host genome. The process of integration can be divided into two sequential reactions. In the first one, named 3'-processing, the enzyme removes di- or trinucleotides from viral DNA ends to expose 3′-hydroxyls attached to the invariant CA dinucleotides. The second step is the insertion of the processed 3′-viral DNA ends into the host chromosomal DNA by a trans-esterification reaction. This is the strand transfer.

== Interaction with LEDGF/p75 and antiviral ==

Research on HIV show that the integrase use a protein, the LEDGF/p75 cofactor, so as to the preintegration complex is ligated to the DNA.
Some recents experimental antiviral inhibe this interaction and unable the integrase to interact with the cofactor. Thus, the DNA wouldn’t be inserted into the genome of the cell.

== Structure ==

HIV-1 integrase is composed of three domains: the N-terminal (residues 1-49), the core domain (residues 50-212) and the C-terminal domain (residues 213-288). The core domain is responsible for the catalytic activity of the enzyme. It contains three acidic residues, the D,D-35-E motif which plays a key role in catalysis. The N-terminal domain includes the conserved HHCC motif, which binds zinc. The C-terminal domain is less well conserved. [http://www.jbc.org/content/276/26/23213/F2.expansion.html]

====Structure and role of the core domain in the integration====

'''The three domain of the HIV integrase:'''

[[Image:Domain_HIV_Integrase.jpg]]

'''HIV Integrase sequence:'''

[[Image:HIV integrase sequenc.jpg]][https://www.uniprot.org/uniprot/Q76353#sequences] Length:288, Mass (Da):32,199

[[Image:HIV Integrase sequence.jpg]]

====Structure and role of the core domain====

====Structure and role of the N ter domain====

The N-terminal domain of HIV-1 integrase contains a conserved pair of His and Cys residues, a motif similar to the zinc-coordinating residues of zinc fingers. This domain binds zinc but its structure is totally different from that of zinc fingers. It consists of a bundle of three α-helices. It has an SH3 fold, although there is no known functional relationship with the SH3 domains of other proteins.

[[Image:Nter-domain.jpg]]

====Structure and interaction with the antiviral====

The new experimental antirviral, here the (6-chloro-2-oxo-4-phenyl-1,2-dihydroquinolin-3-yl)acetic acid, interacts with the site with which <scene name='80/802676/Site_of_interaction/7'>the cofactor bind with the LEDGF/p75 cofactor</scene>. This site is situated in the core domain.
The molecule then inhibits the interaction between the LEDGF/p75 cofactor and the integrase.
The whole complex between the integrase and the cofactor is displayed on the proteopedia page [[2b4j]].

== HIV ==

HIV stands for human immunodeficiency virus. It is a retrovirus virus that damages the cells in the immune system and weakens the ability to fight everyday infections and disease. Copied into DNA, HIV is inserted into the genome of the infected cell thanks to integrases. To replicate and diffuse himself it attacks the body’s immune system, specifically the CD4 cells (T cells), which help fight off infections. As soon as HIV enters an individual, it accumulates in these cells and forms reservoirs of latent viruses in a few days or even hours. These reservoirs persist for life.

No cure currently exists, but HIV can be controlled by using antiretroviral therapy or ART. It is a combination of antiretroviral drugs to maximally suppress the HIV virus and stop the progression of HIV disease. Before the introduction of ART in the mid-1990s, people with HIV could progress to AIDS in just a few years. Today, someone diagnosed with HIV and treated before the disease is far advanced can live nearly as long as someone who does not have HIV.[https://www.hiv.gov/hiv-basics/overview/about-hiv-and-aids/what-are-hiv-and-aids]

== Disease: AIDS ==

AIDS is the ultimate stage of infection with the human immunodeficiency virus. The word AIDS stands for for Acquired Immunodeficiency Syndrome. People with AIDS get an increasing number of severe illnesses, called opportunistic infections, because of there damaged immune system. You are considered to have progressed to AIDS when the number of your CD4 cells falls below 200 cells per cubic millimeter of blood (200 cells/mm3). (In someone with a healthy immune system, CD4 counts are between 500 and 1,600 cells/mm3.) You are also considered to have progressed to AIDS if you develop one or more opportunistic illnesses, regardless of your CD4 count.[https://www.hiv.gov/hiv-basics/overview/about-hiv-and-aids/what-are-hiv-and-aids]

<scene name='80/802676/Hiv_integrase_3lpt/8'>HIV Integrase 3lpt</scene>

==See also==
http://proteopedia.org/wiki/index.php/2b4j :integrase ligated with the cofactor LEDGF/p75

== References ==
https://www.hiv.gov/hiv-basics/overview/about-hiv-and-aids/what-are-hiv-and-aids
https://www-nature-com.scd-rproxy.u-strasbg.fr/articles/nchembio.370
https://www.uniprot.org/uniprot/Q76353#sequences
http://pfam.xfam.org/family/rve
http://pfam.xfam.org/protein/Q76353_9HIV1
https://www.rcsb.org/3d-view/3LPT/1
https://en.wikipedia.org/wiki/Diethylene_glycol
https://microbewiki.kenyon.edu/index.php/HIV-1_Pre-Integration_Complex
https://www.uniprot.org/uniprot/Q76353
https://www.rcsb.org/structure/3lpt
http://proteopedia.org/wiki/index.php/Retroviral_Integrase
<references/>

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<scene name='80/802676/Site_of_interaction/1'>Text To Be Displayed</scene>{{Sandbox_Reserved_ESBS}}
=='''3lpt - HIV integrase'''==

<StructureSection load='3lpt' size='340' side='right' caption='[[3lpt]], [[Resolution|resolution]] 2.00Å' scene=''>
3lt is an integrase of the HIV, the Human Immunodeficiency Virus. An integrase is an enzyme produced by a retrovirus to integrate its genetic material into the DNA of the infected cell. It is one of three enzymes of HIV, the others being the Reverse Transcriptase and the Protease.

== Structural highlights ==
<table><tr><td colspan='2'>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=723:(6-CHLORO-2-OXO-4-PHENYL-1,2-DIHYDROQUINOLIN-3-YL)ACETIC+ACID'>723</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=P03:2-[3-[3-(2-HYDROXYETHOXY)PROPOXY]PROPOXY]ETHANOL'>P03</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CAF:S-DIMETHYLARSINOYL-CYSTEINE'>CAF</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1hyv|1hyv]], [[3lpu|3lpu]]</td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3lpt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3lpt OCA], [http://pdbe.org/3lpt PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3lpt RCSB], [http://www.ebi.ac.uk/pdbsum/3lpt PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3lpt ProSAT]</span></td></tr>
</table>

== Function ==

HIV integrase is an enzyme required for the integration of viral DNA into the host genome. The process of integration can be divided into two sequential reactions. In the first one, named 3'-processing, the enzyme removes di- or trinucleotides from viral DNA ends to expose 3′-hydroxyls attached to the invariant CA dinucleotides. The second step is the insertion of the processed 3′-viral DNA ends into the host chromosomal DNA by a trans-esterification reaction. This is the strand transfer.

== Interaction with LEDGF/p75 and antiviral ==

Research on HIV show that the integrase use a protein, the LEDGF/p75 cofactor, so as to the preintegration complex is ligated to the DNA.
Some recents experimental antiviral inhibe this interaction and unable the integrase to interact with the cofactor. Thus, the DNA wouldn’t be inserted into the genome of the cell.

== Structure ==

HIV-1 integrase is composed of three domains: the N-terminal (residues 1-49), the core domain (residues 50-212) and the C-terminal domain (residues 213-288). The core domain is responsible for the catalytic activity of the enzyme. It contains three acidic residues, the D,D-35-E motif which plays a key role in catalysis. The N-terminal domain includes the conserved HHCC motif, which binds zinc. The C-terminal domain is less well conserved. [http://www.jbc.org/content/276/26/23213/F2.expansion.html]
The complex with the two DNA are displayed on the proteopedia page [[5u1c]].

====Structure and role of the core domain in the integration====

'''The three domain of the HIV integrase:'''

[[Image:Domain_HIV_Integrase.jpg]]

'''HIV Integrase sequence:'''

[[Image:HIV integrase sequenc.jpg]][https://www.uniprot.org/uniprot/Q76353#sequences] Length:288, Mass (Da):32,199

[[Image:HIV Integrase sequence.jpg]]

====Structure and interaction with the antiviral====

The new experimental antirviral, here the (6-chloro-2-oxo-4-phenyl-1,2-dihydroquinolin-3-yl)acetic acid, interacts with the site with which <scene name='80/802676/Site_of_interaction/7'>the cofactor bind with the LEDGF/p75 cofactor</scene>. This site is situated in the core domain.
The molecule then inhibits the interaction between the LEDGF/p75 cofactor and the integrase.
The whole complex between the integrase and the cofactor is displayed on the proteopedia page [[2b4j]].

== HIV ==

HIV stands for human immunodeficiency virus. It is a retrovirus virus that damages the cells in the immune system and weakens the ability to fight everyday infections and disease. Copied into DNA, HIV is inserted into the genome of the infected cell thanks to integrases. To replicate and diffuse himself it attacks the body’s immune system, specifically the CD4 cells (T cells), which help fight off infections. As soon as HIV enters an individual, it accumulates in these cells and forms reservoirs of latent viruses in a few days or even hours. These reservoirs persist for life.

No cure currently exists, but HIV can be controlled by using antiretroviral therapy or ART. It is a combination of antiretroviral drugs to maximally suppress the HIV virus and stop the progression of HIV disease. Before the introduction of ART in the mid-1990s, people with HIV could progress to AIDS in just a few years. Today, someone diagnosed with HIV and treated before the disease is far advanced can live nearly as long as someone who does not have HIV.[https://www.hiv.gov/hiv-basics/overview/about-hiv-and-aids/what-are-hiv-and-aids]

== Disease: AIDS ==

AIDS is the ultimate stage of infection with the human immunodeficiency virus. The word AIDS stands for for Acquired Immunodeficiency Syndrome. People with AIDS get an increasing number of severe illnesses, called opportunistic infections, because of there damaged immune system. You are considered to have progressed to AIDS when the number of your CD4 cells falls below 200 cells per cubic millimeter of blood (200 cells/mm3). (In someone with a healthy immune system, CD4 counts are between 500 and 1,600 cells/mm3.) You are also considered to have progressed to AIDS if you develop one or more opportunistic illnesses, regardless of your CD4 count.[https://www.hiv.gov/hiv-basics/overview/about-hiv-and-aids/what-are-hiv-and-aids]

<scene name='80/802676/Hiv_integrase_3lpt/8'>HIV Integrase 3lpt</scene>

==See also==
http://proteopedia.org/wiki/index.php/2b4j :integrase ligated with the cofactor LEDGF/p75
http://proteopedia.org/wiki/index.php/5u1c : integrase complex with the two DNAs

== References ==
https://www.hiv.gov/hiv-basics/overview/about-hiv-and-aids/what-are-hiv-and-aids
https://www-nature-com.scd-rproxy.u-strasbg.fr/articles/nchembio.370
https://www.uniprot.org/uniprot/Q76353#sequences
http://pfam.xfam.org/family/rve
http://pfam.xfam.org/protein/Q76353_9HIV1
https://www.rcsb.org/3d-view/3LPT/1
https://en.wikipedia.org/wiki/Diethylene_glycol
https://microbewiki.kenyon.edu/index.php/HIV-1_Pre-Integration_Complex
https://www.uniprot.org/uniprot/Q76353
https://www.rcsb.org/structure/3lpt
http://proteopedia.org/wiki/index.php/Retroviral_Integrase
<references/>

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{{Sandbox_Reserved_ESBS}}
=='''3lpt - HIV integrase'''==

<StructureSection load='3lpt' size='340' side='right' caption='[[3lpt]], [[Resolution|resolution]] 2.00Å' scene=''>
3lt is an integrase of the HIV, the Human Immunodeficiency Virus. An integrase is an enzyme produced by a retrovirus to integrate its genetic material into the DNA of the infected cell. It is one of three enzymes of HIV, the others being the Reverse Transcriptase and the Protease.

== Structural highlights ==
<table><tr><td colspan='2'>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=723:(6-CHLORO-2-OXO-4-PHENYL-1,2-DIHYDROQUINOLIN-3-YL)ACETIC+ACID'>723</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=P03:2-[3-[3-(2-HYDROXYETHOXY)PROPOXY]PROPOXY]ETHANOL'>P03</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CAF:S-DIMETHYLARSINOYL-CYSTEINE'>CAF</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1hyv|1hyv]], [[3lpu|3lpu]]</td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3lpt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3lpt OCA], [http://pdbe.org/3lpt PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3lpt RCSB], [http://www.ebi.ac.uk/pdbsum/3lpt PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3lpt ProSAT]</span></td></tr>
</table>

== Function ==

HIV integrase is an enzyme required for the integration of viral DNA into the host genome. The process of integration can be divided into two sequential reactions. In the first one, named 3'-processing, the enzyme removes di- or trinucleotides from viral DNA ends to expose 3′-hydroxyls attached to the invariant CA dinucleotides. The second step is the insertion of the processed 3′-viral DNA ends into the host chromosomal DNA by a trans-esterification reaction. This is the strand transfer.

== Interaction with LEDGF/p75 and antiviral ==

Research on HIV show that the integrase use a protein, the LEDGF/p75 cofactor, so as to the preintegration complex is ligated to the DNA.
Some recents experimental antiviral inhibe this interaction and unable the integrase to interact with the cofactor. Thus, the DNA wouldn’t be inserted into the genome of the cell.

== Structure ==

HIV-1 integrase is composed of three domains: the N-terminal (residues 1-49), the core domain (residues 50-212) and the C-terminal domain (residues 213-288). The core domain is responsible for the catalytic activity of the enzyme. It contains three acidic residues, the D,D-35-E motif which plays a key role in catalysis. The N-terminal domain includes the conserved HHCC motif, which binds zinc. The C-terminal domain is less well conserved. [http://www.jbc.org/content/276/26/23213/F2.expansion.html]

====Structure and role of the core domain in the integration====

'''The three domain of the HIV integrase:'''

[[Image:Domain_HIV_Integrase.jpg]]

'''HIV Integrase sequence:'''

[[Image:HIV integrase sequenc.jpg]][https://www.uniprot.org/uniprot/Q76353#sequences] Length:288, Mass (Da):32,199

[[Image:HIV Integrase sequence.jpg]]

====Structure and interaction with the antiviral====

The new experimental antirviral, here the (6-chloro-2-oxo-4-phenyl-1,2-dihydroquinolin-3-yl)acetic acid, interacts with which bind to the LEDGF/p75 cofactor. This site is situated in the core domain.
The molecule

== HIV ==

HIV stands for human immunodeficiency virus. It is a retrovirus virus that damages the cells in the immune system and weakens the ability to fight everyday infections and disease. Copied into DNA, HIV is inserted into the genome of the infected cell thanks to integrases. To replicate and diffuse himself it attacks the body’s immune system, specifically the CD4 cells (T cells), which help fight off infections. As soon as HIV enters an individual, it accumulates in these cells and forms reservoirs of latent viruses in a few days or even hours. These reservoirs persist for life.

No cure currently exists, but HIV can be controlled by using antiretroviral therapy or ART. It is a combination of antiretroviral drugs to maximally suppress the HIV virus and stop the progression of HIV disease. Before the introduction of ART in the mid-1990s, people with HIV could progress to AIDS in just a few years. Today, someone diagnosed with HIV and treated before the disease is far advanced can live nearly as long as someone who does not have HIV.[https://www.hiv.gov/hiv-basics/overview/about-hiv-and-aids/what-are-hiv-and-aids]

== Disease: AIDS ==

AIDS is the ultimate stage of infection with the human immunodeficiency virus. The word AIDS stands for for Acquired Immunodeficiency Syndrome. People with AIDS get an increasing number of severe illnesses, called opportunistic infections, because of there damaged immune system. You are considered to have progressed to AIDS when the number of your CD4 cells falls below 200 cells per cubic millimeter of blood (200 cells/mm3). (In someone with a healthy immune system, CD4 counts are between 500 and 1,600 cells/mm3.) You are also considered to have progressed to AIDS if you develop one or more opportunistic illnesses, regardless of your CD4 count.[https://www.hiv.gov/hiv-basics/overview/about-hiv-and-aids/what-are-hiv-and-aids]

<scene name='80/802676/Hiv_integrase_3lpt/8'>HIV Integrase 3lpt</scene>
== References ==
https://www.hiv.gov/hiv-basics/overview/about-hiv-and-aids/what-are-hiv-and-aids
https://www-nature-com.scd-rproxy.u-strasbg.fr/articles/nchembio.370
https://www.uniprot.org/uniprot/Q76353#sequences
<references/>

Sandbox Reserved 1502

2019-01-10T17:34:51Z

Severine Perrin:

{{Sandbox_Reserved_ESBS}}
=='''3lpt - HIV integrase'''==

<StructureSection load='3lpt' size='340' side='right' caption='[[3lpt]], [[Resolution|resolution]] 2.00Å' scene=''>
3lt is an integrase of the HIV, the Human Immunodeficiency Virus. An integrase is an enzyme produced by a retrovirus to integrate its genetic material into the DNA of the infected cell. It is one of three enzymes of HIV, the others being the Reverse Transcriptase and the Protease.

== Structural highlights ==
<table><tr><td colspan='2'>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=723:(6-CHLORO-2-OXO-4-PHENYL-1,2-DIHYDROQUINOLIN-3-YL)ACETIC+ACID'>723</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=P03:2-[3-[3-(2-HYDROXYETHOXY)PROPOXY]PROPOXY]ETHANOL'>P03</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CAF:S-DIMETHYLARSINOYL-CYSTEINE'>CAF</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1hyv|1hyv]], [[3lpu|3lpu]]</td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3lpt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3lpt OCA], [http://pdbe.org/3lpt PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3lpt RCSB], [http://www.ebi.ac.uk/pdbsum/3lpt PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3lpt ProSAT]</span></td></tr>
</table>

== Function ==

HIV integrase is an enzyme required for the integration of viral DNA into the host genome. The process of integration can be divided into two sequential reactions. In the first one, named 3'-processing, the enzyme removes di- or trinucleotides from viral DNA ends to expose 3′-hydroxyls attached to the invariant CA dinucleotides. The second step is the insertion of the processed 3′-viral DNA ends into the host chromosomal DNA by a trans-esterification reaction. This is the strand transfer.

== Interaction with LEDGF/p75 and antiviral ==

Research on HIV show that the integrase use a protein, the LEDGF/p75 cofactor, so as to the preintegration complex is ligated to the DNA.
Some recents experimental antiviral inhibe this interaction and unable the integrase to interact with the cofactor. Thus, the DNA wouldn’t be inserted into the genome of the cell.

== Structure ==

HIV-1 integrase is composed of three domains: the N-terminal (residues 1-49), the core domain (residues 50-212) and the C-terminal domain (residues 213-288). The core domain is responsible for the catalytic activity of the enzyme. It contains three acidic residues, the D,D-35-E motif which plays a key role in catalysis. The N-terminal domain includes the conserved HHCC motif, which binds zinc. The C-terminal domain is less well conserved. [http://www.jbc.org/content/276/26/23213/F2.expansion.html]

====Structure and role of the core domain in the integration====

'''The three domain of the HIV integrase:'''

[[Image:Domain_HIV_Integrase.jpg]]

'''HIV Integrase sequence:'''

[[Image:HIV integrase sequenc.jpg]][https://www.uniprot.org/uniprot/Q76353#sequences] Length:288, Mass (Da):32,199

[[Image:HIV Integrase sequence.jpg]]

====Structure and interaction with the antiviral====

The new experimental antirviral, here the (6-chloro-2-oxo-4-phenyl-1,2-dihydroquinolin-3-yl)acetic acid, interacts with ==Your Heading Here (maybe something like 'Structure')==
<StructureSection load='3rec' size='350' side='right' caption='Escherichia coli reca protein-bound DNA (PDB entry [[3rec]])' scene=''>the site</StructureSection> which bind to the LEDGF/p75 cofactor. This site is situated in the core domain.
The molecule

== HIV ==

HIV stands for human immunodeficiency virus. It is a retrovirus virus that damages the cells in the immune system and weakens the ability to fight everyday infections and disease. Copied into DNA, HIV is inserted into the genome of the infected cell thanks to integrases. To replicate and diffuse himself it attacks the body’s immune system, specifically the CD4 cells (T cells), which help fight off infections. As soon as HIV enters an individual, it accumulates in these cells and forms reservoirs of latent viruses in a few days or even hours. These reservoirs persist for life.

No cure currently exists, but HIV can be controlled by using antiretroviral therapy or ART. It is a combination of antiretroviral drugs to maximally suppress the HIV virus and stop the progression of HIV disease. Before the introduction of ART in the mid-1990s, people with HIV could progress to AIDS in just a few years. Today, someone diagnosed with HIV and treated before the disease is far advanced can live nearly as long as someone who does not have HIV.[https://www.hiv.gov/hiv-basics/overview/about-hiv-and-aids/what-are-hiv-and-aids]

== Disease: AIDS ==

AIDS is the ultimate stage of infection with the human immunodeficiency virus. The word AIDS stands for for Acquired Immunodeficiency Syndrome. People with AIDS get an increasing number of severe illnesses, called opportunistic infections, because of there damaged immune system. You are considered to have progressed to AIDS when the number of your CD4 cells falls below 200 cells per cubic millimeter of blood (200 cells/mm3). (In someone with a healthy immune system, CD4 counts are between 500 and 1,600 cells/mm3.) You are also considered to have progressed to AIDS if you develop one or more opportunistic illnesses, regardless of your CD4 count.[https://www.hiv.gov/hiv-basics/overview/about-hiv-and-aids/what-are-hiv-and-aids]

<scene name='80/802676/Hiv_integrase_3lpt/8'>HIV Integrase 3lpt</scene>
== References ==
https://www.hiv.gov/hiv-basics/overview/about-hiv-and-aids/what-are-hiv-and-aids
https://www-nature-com.scd-rproxy.u-strasbg.fr/articles/nchembio.370
https://www.uniprot.org/uniprot/Q76353#sequences
<references/>