5mma - Revision history

OCA at 17:38, 8 November 2023

OCA — Wed, 08 Nov 2023 17:38:12 GMT

←Older revision		Revision as of 17:38, 8 November 2023
Line 3:		Line 3:
	<StructureSection load='5mma' size='340' side='right'caption='[[5mma]], [[Resolution\|resolution]] 2.55Å' scene=''>		<StructureSection load='5mma' size='340' side='right'caption='[[5mma]], [[Resolution\|resolution]] 2.55Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5mma]] is a 4 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~Foamv Foamv~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5MMA OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=5MMA FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5mma]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Human_spumaretrovirus Human spumaretrovirus] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5MMA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5MMA FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=HEZ:HEXANE-1,6-DIOL'>HEZ</scene>, <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=VHT:methyl+2-[[3-[[2,4-bis(fluoranyl)phenyl]methylcarbamoyl]-1-oxidanyl-2-oxidanylidene-1,8-naphthyridin-4-yl]amino]ethanoate'>VHT</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene>~~</td></tr>~~	+	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution\|Resolution]] 2.55Å</td></tr>
-	~~<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">pol ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=11963 FOAMV])~~</td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=HEZ:HEXANE-1,6-DIOL'>HEZ</scene>, <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=VHT:methyl+2-[[3-[[2,4-bis(fluoranyl)phenyl]methylcarbamoyl]-1-oxidanyl-2-oxidanylidene-1,8-naphthyridin-4-yl]amino]ethanoate'>VHT</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://proteopedia.org/fgij/fg.htm?mol=5mma FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5mma OCA], [~~http~~://pdbe.org/5mma PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5mma RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5mma PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5mma ProSAT]</span></td></tr>	+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5mma FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5mma OCA], [https://pdbe.org/5mma PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5mma RCSB], [https://www.ebi.ac.uk/pdbsum/5mma PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5mma ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/POL_FOAMV POL_FOAMV]] The aspartyl protease activity mediates proteolytic cleavages of Gag and Pol polyproteins. The reverse transcriptase (RT) activity converts the viral RNA genome into dsDNA in the cytoplasm, shortly after virus entry into the cell (early reverse transcription) or after proviral DNA transcription (late reverse transcription). RT consists of a DNA polymerase activity that can copy either DNA or RNA templates, and a ribonuclease H (RNase H) activity that cleaves the RNA strand of RNA-DNA heteroduplexes in a partially processive 3' to 5' endonucleasic mode. Conversion of viral genomic RNA into dsDNA requires many steps. A tRNA-Lys1,2 binds to the primer-binding site (PBS) situated at the 5'-end of the viral RNA. RT uses the 3' end of the tRNA primer to perform a short round of RNA-dependent minus-strand DNA synthesis. The reading proceeds through the U5 region and ends after the repeated (R) region which is present at both ends of viral RNA. The portion of the RNA-DNA heteroduplex is digested by the RNase H, resulting in a ssDNA product attached to the tRNA primer. This ssDNA/tRNA hybridizes with the identical R region situated at the 3' end of viral RNA. This template exchange, known as minus-strand DNA strong stop transfer, can be either intra- or intermolecular. RT uses the 3' end of this newly synthesized short ssDNA to perform the RNA-dependent minus-strand DNA synthesis of the whole template. RNase H digests the RNA template except for a polypurine tract (PPT) situated at the 5'-end and near the center of the genome. It is not clear if both polymerase and RNase H activities are simultaneous. RNase H probably can proceed both in a polymerase-dependent (RNA cut into small fragments by the same RT performing DNA synthesis) and a polymerase-independent mode (cleavage of remaining RNA fragments by free RTs). Secondly, RT performs DNA-directed plus-strand DNA synthesis using the PPT that has not been removed by RNase H as primer. PPT and tRNA primers are then removed by RNase H. The 3' and 5' ssDNA PBS regions hybridize to form a circular dsDNA intermediate. Strand displacement synthesis by RT to the PBS and PPT ends produces a blunt ended, linear dsDNA copy of the viral genome that includes long terminal repeats (LTRs) at both ends (By similarity). Integrase catalyzes viral DNA integration into the host chromosome, by performing a series of DNA cutting and joining reactions. This enzyme activity takes place after virion entry into a cell and reverse transcription of the RNA genome in dsDNA. The first step in the integration process is 3' processing. This step requires a complex comprising at least the viral genome, matrix protein, and integrase. This complex is called the pre-integration complex (PIC). The integrase protein removes 2 nucleotides from the 3' end of the viral DNA right (U5) end, leaving the left (U3) intact. In the second step, the PIC enters cell nucleus. This process is mediated through the integrase and allows the virus to infect both dividing (nuclear membrane disassembled) and G1/S-arrested cells (active translocation), but with no viral gene expression in the latter. In the third step, termed strand transfer, the integrase protein joins the previously processed 3' ends to the 5' ends of strands of target cellular DNA at the site of integration. It is however not clear how integration then proceeds to resolve the asymmetrical cleavage of viral DNA (By similarity).	+	[https://www.uniprot.org/uniprot/POL_FOAMV POL_FOAMV] The aspartyl protease activity mediates proteolytic cleavages of Gag and Pol polyproteins. The reverse transcriptase (RT) activity converts the viral RNA genome into dsDNA in the cytoplasm, shortly after virus entry into the cell (early reverse transcription) or after proviral DNA transcription (late reverse transcription). RT consists of a DNA polymerase activity that can copy either DNA or RNA templates, and a ribonuclease H (RNase H) activity that cleaves the RNA strand of RNA-DNA heteroduplexes in a partially processive 3' to 5' endonucleasic mode. Conversion of viral genomic RNA into dsDNA requires many steps. A tRNA-Lys1,2 binds to the primer-binding site (PBS) situated at the 5'-end of the viral RNA. RT uses the 3' end of the tRNA primer to perform a short round of RNA-dependent minus-strand DNA synthesis. The reading proceeds through the U5 region and ends after the repeated (R) region which is present at both ends of viral RNA. The portion of the RNA-DNA heteroduplex is digested by the RNase H, resulting in a ssDNA product attached to the tRNA primer. This ssDNA/tRNA hybridizes with the identical R region situated at the 3' end of viral RNA. This template exchange, known as minus-strand DNA strong stop transfer, can be either intra- or intermolecular. RT uses the 3' end of this newly synthesized short ssDNA to perform the RNA-dependent minus-strand DNA synthesis of the whole template. RNase H digests the RNA template except for a polypurine tract (PPT) situated at the 5'-end and near the center of the genome. It is not clear if both polymerase and RNase H activities are simultaneous. RNase H probably can proceed both in a polymerase-dependent (RNA cut into small fragments by the same RT performing DNA synthesis) and a polymerase-independent mode (cleavage of remaining RNA fragments by free RTs). Secondly, RT performs DNA-directed plus-strand DNA synthesis using the PPT that has not been removed by RNase H as primer. PPT and tRNA primers are then removed by RNase H. The 3' and 5' ssDNA PBS regions hybridize to form a circular dsDNA intermediate. Strand displacement synthesis by RT to the PBS and PPT ends produces a blunt ended, linear dsDNA copy of the viral genome that includes long terminal repeats (LTRs) at both ends (By similarity). Integrase catalyzes viral DNA integration into the host chromosome, by performing a series of DNA cutting and joining reactions. This enzyme activity takes place after virion entry into a cell and reverse transcription of the RNA genome in dsDNA. The first step in the integration process is 3' processing. This step requires a complex comprising at least the viral genome, matrix protein, and integrase. This complex is called the pre-integration complex (PIC). The integrase protein removes 2 nucleotides from the 3' end of the viral DNA right (U5) end, leaving the left (U3) intact. In the second step, the PIC enters cell nucleus. This process is mediated through the integrase and allows the virus to infect both dividing (nuclear membrane disassembled) and G1/S-arrested cells (active translocation), but with no viral gene expression in the latter. In the third step, termed strand transfer, the integrase protein joins the previously processed 3' ends to the 5' ends of strands of target cellular DNA at the site of integration. It is however not clear how integration then proceeds to resolve the asymmetrical cleavage of viral DNA (By similarity).
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 26:		Line 26:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Foamv~~]]	+	[[Category: Human spumaretrovirus]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: ~~Cherepanov, P~~]]	+	[[Category: Synthetic construct]]
-	[[Category: ~~Maskell, D~~ P]]	+	[[Category: Cherepanov P]]
-	[[Category: ~~Pye, V E~~]]	+	[[Category: Maskell DP]]
-	[[Category: ~~Drug]]~~	+	[[Category: Pye VE]]
-	~~[[Category: Hiv]]~~	+
-	~~[[Category: Inhibitor]]~~	+
-	~~[[Category: Insti]]~~	+
-	~~[[Category: Integrase]]~~	+
-	~~[[Category: Integration]]~~	+
-	~~[[Category: Pfv]]~~	+
-	~~[[Category: Prototype foamy virus]]~~	+
-	~~[[Category: Strand transfer]]~~	+
-	~~[[Category: Tetramer intasome]]~~	+
-	~~[[Category: Viral protein~~]]	+

OCA at 07:16, 30 September 2020

OCA — Wed, 30 Sep 2020 07:16:25 GMT

←Older revision		Revision as of 07:16, 30 September 2020
Line 1:		Line 1:

	==Crystal structure of the Prototype Foamy Virus (PFV) intasome in complex with magnesium and the INSTI XZ379 (compound 5'g)==		==Crystal structure of the Prototype Foamy Virus (PFV) intasome in complex with magnesium and the INSTI XZ379 (compound 5'g)==
-	<StructureSection load='5mma' size='340' side='right' caption='[[5mma]], [[Resolution\|resolution]] 2.55Å' scene=''>	+	<StructureSection load='5mma' size='340' side='right'caption='[[5mma]], [[Resolution\|resolution]] 2.55Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5mma]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Foamv Foamv]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5MMA OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5MMA FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5mma]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Foamv Foamv]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5MMA OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5MMA FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=HEZ:HEXANE-1,6-DIOL'>HEZ</scene>, <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=VHT:methyl+2-[[3-[[2,4-bis(fluoranyl)phenyl]methylcarbamoyl]-1-oxidanyl-2-oxidanylidene-1,8-naphthyridin-4-yl]amino]ethanoate'>VHT</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=HEZ:HEXANE-1,6-DIOL'>HEZ</scene>, <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=VHT:methyl+2-[[3-[[2,4-bis(fluoranyl)phenyl]methylcarbamoyl]-1-oxidanyl-2-oxidanylidene-1,8-naphthyridin-4-yl]amino]ethanoate'>VHT</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">pol ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=11963 FOAMV])</td></tr>		<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">pol ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=11963 FOAMV])</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=5mma FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5mma OCA], [http://pdbe.org/5mma PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5mma RCSB], [http://www.ebi.ac.uk/pdbsum/5mma PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5mma ProSAT]</span></td></tr>	+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5mma FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5mma OCA], [http://pdbe.org/5mma PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5mma RCSB], [http://www.ebi.ac.uk/pdbsum/5mma PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5mma ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 19:		Line 19:
	</div>		</div>
	<div class="pdbe-citations 5mma" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5mma" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Retroviral integrase 3D structures\|Retroviral integrase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
Line 24:		Line 27:
	</StructureSection>		</StructureSection>
	[[Category: Foamv]]		[[Category: Foamv]]
		+	[[Category: Large Structures]]
	[[Category: Cherepanov, P]]		[[Category: Cherepanov, P]]
	[[Category: Maskell, D P]]		[[Category: Maskell, D P]]

OCA at 13:06, 6 November 2017

OCA — Mon, 06 Nov 2017 13:06:51 GMT

←Older revision		Revision as of 13:06, 6 November 2017
Line 3:		Line 3:
	<StructureSection load='5mma' size='340' side='right' caption='[[5mma]], [[Resolution\|resolution]] 2.55Å' scene=''>		<StructureSection load='5mma' size='340' side='right' caption='[[5mma]], [[Resolution\|resolution]] 2.55Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5mma]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5MMA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5MMA FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5mma]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Foamv Foamv]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5MMA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5MMA FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=HEZ:HEXANE-1,6-DIOL'>HEZ</scene>, <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=VHT:methyl+2-[[3-[[2,4-bis(fluoranyl)phenyl]methylcarbamoyl]-1-oxidanyl-2-oxidanylidene-1,8-naphthyridin-4-yl]amino]ethanoate'>VHT</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=HEZ:HEXANE-1,6-DIOL'>HEZ</scene>, <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=VHT:methyl+2-[[3-[[2,4-bis(fluoranyl)phenyl]methylcarbamoyl]-1-oxidanyl-2-oxidanylidene-1,8-naphthyridin-4-yl]amino]ethanoate'>VHT</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">pol ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=11963 FOAMV])</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=5mma FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5mma OCA], [http://pdbe.org/5mma PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5mma RCSB], [http://www.ebi.ac.uk/pdbsum/5mma PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5mma ProSAT]</span></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=5mma FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5mma OCA], [http://pdbe.org/5mma PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5mma RCSB], [http://www.ebi.ac.uk/pdbsum/5mma PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5mma ProSAT]</span></td></tr>
	</table>		</table>
Line 22:		Line 23:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Foamv]]
	[[Category: Cherepanov, P]]		[[Category: Cherepanov, P]]
	[[Category: Maskell, D P]]		[[Category: Maskell, D P]]

OCA at 04:01, 4 August 2017

OCA — Fri, 04 Aug 2017 04:01:02 GMT

←Older revision		Revision as of 04:01, 4 August 2017
Line 1:		Line 1:
-	'''Unreleased structure'''

-	The entry ~~5mma~~ is ~~ON HOLD~~ ~~until Paper~~ Publication	+	==Crystal structure of the Prototype Foamy Virus (PFV) intasome in complex with magnesium and the INSTI XZ379 (compound 5'g)==
		+	<StructureSection load='5mma' size='340' side='right' caption='[[5mma]], [[Resolution\|resolution]] 2.55Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[5mma]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5MMA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5MMA FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=HEZ:HEXANE-1,6-DIOL'>HEZ</scene>, <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=VHT:methyl+2-[[3-[[2,4-bis(fluoranyl)phenyl]methylcarbamoyl]-1-oxidanyl-2-oxidanylidene-1,8-naphthyridin-4-yl]amino]ethanoate'>VHT</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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=5mma FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5mma OCA], [http://pdbe.org/5mma PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5mma RCSB], [http://www.ebi.ac.uk/pdbsum/5mma PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5mma ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/POL_FOAMV POL_FOAMV]] The aspartyl protease activity mediates proteolytic cleavages of Gag and Pol polyproteins. The reverse transcriptase (RT) activity converts the viral RNA genome into dsDNA in the cytoplasm, shortly after virus entry into the cell (early reverse transcription) or after proviral DNA transcription (late reverse transcription). RT consists of a DNA polymerase activity that can copy either DNA or RNA templates, and a ribonuclease H (RNase H) activity that cleaves the RNA strand of RNA-DNA heteroduplexes in a partially processive 3' to 5' endonucleasic mode. Conversion of viral genomic RNA into dsDNA requires many steps. A tRNA-Lys1,2 binds to the primer-binding site (PBS) situated at the 5'-end of the viral RNA. RT uses the 3' end of the tRNA primer to perform a short round of RNA-dependent minus-strand DNA synthesis. The reading proceeds through the U5 region and ends after the repeated (R) region which is present at both ends of viral RNA. The portion of the RNA-DNA heteroduplex is digested by the RNase H, resulting in a ssDNA product attached to the tRNA primer. This ssDNA/tRNA hybridizes with the identical R region situated at the 3' end of viral RNA. This template exchange, known as minus-strand DNA strong stop transfer, can be either intra- or intermolecular. RT uses the 3' end of this newly synthesized short ssDNA to perform the RNA-dependent minus-strand DNA synthesis of the whole template. RNase H digests the RNA template except for a polypurine tract (PPT) situated at the 5'-end and near the center of the genome. It is not clear if both polymerase and RNase H activities are simultaneous. RNase H probably can proceed both in a polymerase-dependent (RNA cut into small fragments by the same RT performing DNA synthesis) and a polymerase-independent mode (cleavage of remaining RNA fragments by free RTs). Secondly, RT performs DNA-directed plus-strand DNA synthesis using the PPT that has not been removed by RNase H as primer. PPT and tRNA primers are then removed by RNase H. The 3' and 5' ssDNA PBS regions hybridize to form a circular dsDNA intermediate. Strand displacement synthesis by RT to the PBS and PPT ends produces a blunt ended, linear dsDNA copy of the viral genome that includes long terminal repeats (LTRs) at both ends (By similarity). Integrase catalyzes viral DNA integration into the host chromosome, by performing a series of DNA cutting and joining reactions. This enzyme activity takes place after virion entry into a cell and reverse transcription of the RNA genome in dsDNA. The first step in the integration process is 3' processing. This step requires a complex comprising at least the viral genome, matrix protein, and integrase. This complex is called the pre-integration complex (PIC). The integrase protein removes 2 nucleotides from the 3' end of the viral DNA right (U5) end, leaving the left (U3) intact. In the second step, the PIC enters cell nucleus. This process is mediated through the integrase and allows the virus to infect both dividing (nuclear membrane disassembled) and G1/S-arrested cells (active translocation), but with no viral gene expression in the latter. In the third step, termed strand transfer, the integrase protein joins the previously processed 3' ends to the 5' ends of strands of target cellular DNA at the site of integration. It is however not clear how integration then proceeds to resolve the asymmetrical cleavage of viral DNA (By similarity).
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Integrase mutations can reduce effectiveness of the first-generation FDA-approved integrase strand transfer inhibitors (INSTIs), raltegravir (RAL) and elvitegravir (EVG). The second-generation agent, dolutegravir (DTG) has enjoyed considerable clinical success; however, resistance-causing mutations that diminish the efficacy of DTG have appeared. Our current findings support and extend the substrate envelope concept that broadly effective INSTIs can be designed by filling the envelope defined by the DNA substrates. Previously, we explored 1-hydroxy-2-oxo-1,2-dihydro-1,8-naphthyridine-3-carboxamides as an INSTI scaffold, making a limited set of derivatives, and concluded that broadly effective INSTIs can be developed using this scaffold. Herein, we report an extended investigation of 6-substituents as well the first examples of 7-substituted analogs of this scaffold. While 7-substituents are not well-tolerated, we have identified novel substituents at the 6-position that are highly effective, with the best compound (6p) retaining better efficacy against a broad panel of known INSTI resistant mutants than any analogs we have previously described.

-	~~Authors:~~ Maskell, ~~D.P.~~, Pye, ~~V.E.~~, ~~Cherepanov~~, P.	+	Structure-Guided Optimization of HIV Integrase Strand Transfer Inhibitors.,Zhao XZ, Smith SJ, Maskell DP, Metifiot M, Pye VE, Fesen K, Marchand C, Pommier Y, Cherepanov P, Hughes SH, Burke TR J Med Chem. 2017 Jul 24. doi: 10.1021/acs.jmedchem.7b00596. PMID:28737946<ref>PMID:28737946</ref>

-	~~Description: Crystal structure~~ of the ~~Prototype Foamy Virus (PFV) intasome in complex with magnesium and the INSTI XZ379 (compound 5'g)~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[Category: Unreleased Structures]]~~	+	</div>
-	~~[[Category~~: ~~Pye, V.E]]~~	+	<div class="pdbe-citations 5mma" style="background-color:#fffaf0;"></div>
-	~~[[Category: Maskell, D.P]]~~	+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
	[[Category: Cherepanov, P]]		[[Category: Cherepanov, P]]
		+	[[Category: Maskell, D P]]
		+	[[Category: Pye, V E]]
		+	[[Category: Drug]]
		+	[[Category: Hiv]]
		+	[[Category: Inhibitor]]
		+	[[Category: Insti]]
		+	[[Category: Integrase]]
		+	[[Category: Integration]]
		+	[[Category: Pfv]]
		+	[[Category: Prototype foamy virus]]
		+	[[Category: Strand transfer]]
		+	[[Category: Tetramer intasome]]
		+	[[Category: Viral protein]]

OCA at 16:34, 15 March 2017

OCA — Wed, 15 Mar 2017 16:34:55 GMT

←Older revision		Revision as of 16:34, 15 March 2017
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	Authors: Maskell, D.P., Pye, V.E., Cherepanov, P.		Authors: Maskell, D.P., Pye, V.E., Cherepanov, P.

-	Description: Crystal structure of the Prototype Foamy Virus (PFV) intasome in complex with magnesium and the INSTI XZ379 (compound 5'p)	+	Description: Crystal structure of the Prototype Foamy Virus (PFV) intasome in complex with magnesium and the INSTI XZ379 (compound 5'g)
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
	[[Category: Pye, V.E]]		[[Category: Pye, V.E]]
	[[Category: Maskell, D.P]]		[[Category: Maskell, D.P]]
	[[Category: Cherepanov, P]]		[[Category: Cherepanov, P]]

OCA at 11:26, 9 March 2017

OCA — Thu, 09 Mar 2017 11:26:35 GMT

←Older revision		Revision as of 11:26, 9 March 2017
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	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
	[[Category: Pye, V.E]]		[[Category: Pye, V.E]]
-	[[Category: Cherepanov, P]]
	[[Category: Maskell, D.P]]		[[Category: Maskell, D.P]]
		+	[[Category: Cherepanov, P]]

OCA at 19:09, 22 December 2016

OCA — Thu, 22 Dec 2016 19:09:44 GMT

←Older revision		Revision as of 19:09, 22 December 2016
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 5mma is ON HOLD	+	The entry 5mma is ON HOLD until Paper Publication

-	Authors: Maskell, D.P., Pye, V. E. , Cherepanov, P.	+	Authors: Maskell, D.P., Pye, V.E., Cherepanov, P.

	Description: Crystal structure of the Prototype Foamy Virus (PFV) intasome in complex with magnesium and the INSTI XZ379 (compound 5'p)		Description: Crystal structure of the Prototype Foamy Virus (PFV) intasome in complex with magnesium and the INSTI XZ379 (compound 5'p)
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
		+	[[Category: Pye, V.E]]
		+	[[Category: Cherepanov, P]]
	[[Category: Maskell, D.P]]		[[Category: Maskell, D.P]]
-	[[Category: Pye, V. E. , Cherepanov, P]]

OCA: Protected "5mma" [edit=sysop:move=sysop]

OCA — Thu, 15 Dec 2016 16:30:06 GMT

Protected "5mma" [edit=sysop:move=sysop]

←Older revision

Revision as of 16:30, 15 December 2016

OCA: New page: '''Unreleased structure''' The entry 5mma is ON HOLD Authors: Maskell, D.P., Pye, V. E. , Cherepanov, P. Description: Crystal structure of the Prototype Foamy Virus (PFV) intasome in c...

OCA — Thu, 15 Dec 2016 16:30:04 GMT

New page: '''Unreleased structure''' The entry 5mma is ON HOLD Authors: Maskell, D.P., Pye, V. E. , Cherepanov, P. Description: Crystal structure of the Prototype Foamy Virus (PFV) intasome in c...

New page

'''Unreleased structure'''

The entry 5mma is ON HOLD

Authors: Maskell, D.P., Pye, V. E. , Cherepanov, P.

Description: Crystal structure of the Prototype Foamy Virus (PFV) intasome in complex with magnesium and the INSTI XZ379 (compound 5'p)
[[Category: Unreleased Structures]]
[[Category: Maskell, D.P]]
[[Category: Pye, V. E. , Cherepanov, P]]