2qi3 - Revision history

OCA at 11:33, 30 August 2023

2023-08-30T11:33:02Z

←Older revision		Revision as of 11:33, 30 August 2023
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	<StructureSection load='2qi3' size='340' side='right'caption='[[2qi3]], [[Resolution\|resolution]] 1.95Å' scene=''>		<StructureSection load='2qi3' size='340' side='right'caption='[[2qi3]], [[Resolution\|resolution]] 1.95Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[2qi3]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/~~9hiv1 9hiv1~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2QI3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2QI3 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[2qi3]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human_immunodeficiency_virus_1 Human immunodeficiency virus 1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2QI3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2QI3 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MZ5:(2S)-N-[(1S,2R)-3-{(1,3-BENZOTHIAZOL-6-YLSULFONYL)[(2S)-2-METHYLBUTYL]AMINO}-1-BENZYL-2-HYDROXYPROPYL]-2-HYDROXY-3-METHYLBUTANAMIDE'>MZ5</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</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]] 1.95Å</td></tr>
-	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2qhy\|2qhy]], [[2qhz\|2qhz]], [[2qi0\|2qi0]], [[2qi1\|2qi1]], [[2qi4\|2qi4]], [[2qi5\|2qi5]], [[2qi6\|2qi6]], [[2qi7\|2qi7]]</div></td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MZ5:(2S)-N-[(1S,2R)-3-{(1,3-BENZOTHIAZOL-6-YLSULFONYL)[(2S)-2-METHYLBUTYL]AMINO}-1-BENZYL-2-HYDROXYPROPYL]-2-HYDROXY-3-METHYLBUTANAMIDE'>MZ5</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr>
-	~~<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">pol ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=11676 9HIV1])~~</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=2qi3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2qi3 OCA], [https://pdbe.org/2qi3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2qi3 RCSB], [https://www.ebi.ac.uk/pdbsum/2qi3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2qi3 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=2qi3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2qi3 OCA], [https://pdbe.org/2qi3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2qi3 RCSB], [https://www.ebi.ac.uk/pdbsum/2qi3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2qi3 ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/POL_HV1A2 POL_HV1A2] Gag-Pol polyprotein and Gag polyprotein may regulate their own translation, by the binding genomic RNA in the 5'-UTR. At low concentration, Gag-Pol and Gag would promote translation, whereas at high concentration, the polyproteins encapsidate genomic RNA and then shutt off translation (By similarity). Matrix protein p17 has two main functions: in infected cell, it targets Gag and Gag-pol polyproteins to the plasma membrane via a multipartite membrane-binding signal, that includes its myristoylated N-terminus. The second function is to play a role in nuclear localization of the viral genome at the very start of cell infection. Matrix protein is the part of the pre-integration complex. It binds in the cytoplasm the human BAF protein which prevent autointegration of the viral genome, and might be included in virions at the ration of zero to 3 BAF dimer per virion. The myristoylation signal and the NLS thus exert conflicting influences its subcellular localization. The key regulation of these motifs might be phosphorylation of a portion of MA molecules on the C-terminal tyrosine at the time of virus maturation, by virion-associated cellular tyrosine kinase. Implicated in the release from host cell mediated by Vpu (By similarity). Capsid protein p24 forms the conical core that encapsulates the genomic RNA-nucleocapsid complex in the virion. Most core are conical, with only 7% tubular. The core is constituted by capsid protein hexamer subunits. The core is disassembled soon after virion entry. Interaction with human PPIA/CYPA protects the virus from restriction by human TRIM5-alpha and from an unknown antiviral activity in human cells. This capsid restriction by TRIM5 is one of the factors which restricts HIV-1 to the human species (By similarity). Nucleocapsid protein p7 encapsulates and protects viral dimeric unspliced (genomic) RNA. Binds these RNAs through its zinc fingers. Facilitates rearangement of nucleic acid secondary structure during retrotranscription of genomic RNA. This capability is referred to as nucleic acid chaperone activity (By similarity). The aspartyl protease mediates proteolytic cleavages of Gag and Gag-Pol polyproteins during or shortly after the release of the virion from the plasma membrane. Cleavages take place as an ordered, step-wise cascade to yield mature proteins. This process is called maturation. Displays maximal activity during the budding process just prior to particle release from the cell. Also cleaves Nef and Vif, probably concomitantly with viral structural proteins on maturation of virus particles (By similarity). Reverse transcriptase/ribonuclease H (RT) is a multifunctional enzyme that converts the viral RNA genome into dsDNA in the cytoplasm, shortly after virus entry into the cell. This enzyme displays 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(3)-Lys 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 two polypurine tracts (PPTs) 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 PPTs that have not been removed by RNase H as primers. PPTs 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 the viral genome, matrix protein, Vpr and integrase. This complex is called the pre-integration complex (PIC). The integrase protein removes 2 nucleotides from each 3' end of the viral DNA, leaving recessed CA OH's at the 3' ends. In the second step, the PIC enters cell nucleus. This process is mediated through integrase and Vpr proteins, and allows the virus to infect a non dividing cell. This ability to enter the nucleus is specific of lentiviruses, other retroviruses cannot and rely on cell division to access cell chromosomes. 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. The 5'-ends are produced by integrase-catalyzed staggered cuts, 5 bp apart. A Y-shaped, gapped, recombination intermediate results, with the 5'-ends of the viral DNA strands and the 3' ends of target DNA strands remaining unjoined, flanking a gap of 5 bp. The last step is viral DNA integration into host chromosome. This involves host DNA repair synthesis in which the 5 bp gaps between the unjoined strands are filled in and then ligated. Since this process occurs at both cuts flanking the HIV genome, a 5 bp duplication of host DNA is produced at the ends of HIV-1 integration. Alternatively, Integrase may catalyze the excision of viral DNA just after strand transfer, this is termed disintegration (By similarity).
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human immunodeficiency virus 1]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Nalam~~, M N.L~~]]	+	[[Category: Nalam MNL]]
-	[[Category: Schiffer~~, C A]]~~	+	[[Category: Schiffer CA]]
-	~~[[Category: Drug design]]~~	+
-	~~[[Category: Hiv-1 protease]]~~	+
-	~~[[Category: Hydrolase]]~~	+
-	~~[[Category: Protease inhibitor~~]]	+

OCA at 08:20, 25 June 2021

2021-06-25T08:20:47Z

←Older revision		Revision as of 08:20, 25 June 2021
Line 1:		Line 1:

	==Crystal structure of protease inhibitor, MIT-2-AD94 in complex with wild type HIV-1 protease==		==Crystal structure of protease inhibitor, MIT-2-AD94 in complex with wild type HIV-1 protease==
-	<StructureSection load='2qi3' size='340' side='right' caption='[[2qi3]], [[Resolution\|resolution]] 1.95Å' scene=''>	+	<StructureSection load='2qi3' size='340' side='right'caption='[[2qi3]], [[Resolution\|resolution]] 1.95Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[2qi3]] is a 2 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/9hiv1 9hiv1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2QI3 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=2QI3 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[2qi3]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/9hiv1 9hiv1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2QI3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2QI3 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MZ5:(2S)-N-[(1S,2R)-3-{(1,3-BENZOTHIAZOL-6-YLSULFONYL)[(2S)-2-METHYLBUTYL]AMINO}-1-BENZYL-2-HYDROXYPROPYL]-2-HYDROXY-3-METHYLBUTANAMIDE'>MZ5</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MZ5:(2S)-N-[(1S,2R)-3-{(1,3-BENZOTHIAZOL-6-YLSULFONYL)[(2S)-2-METHYLBUTYL]AMINO}-1-BENZYL-2-HYDROXYPROPYL]-2-HYDROXY-3-METHYLBUTANAMIDE'>MZ5</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr>
-	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2qhy\|2qhy]], [[2qhz\|2qhz]], [[2qi0\|2qi0]], [[2qi1\|2qi1]], [[2qi4\|2qi4]], [[2qi5\|2qi5]], [[2qi6\|2qi6]], [[2qi7\|2qi7]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2qhy\|2qhy]], [[2qhz\|2qhz]], [[2qi0\|2qi0]], [[2qi1\|2qi1]], [[2qi4\|2qi4]], [[2qi5\|2qi5]], [[2qi6\|2qi6]], [[2qi7\|2qi7]]</div></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=11676 9HIV1])</td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">pol ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=11676 9HIV1])</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=2qi3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2qi3 OCA], [~~http~~://pdbe.org/2qi3 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=2qi3 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/2qi3 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=2qi3 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=2qi3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2qi3 OCA], [https://pdbe.org/2qi3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2qi3 RCSB], [https://www.ebi.ac.uk/pdbsum/2qi3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2qi3 ProSAT]</span></td></tr>
	</table>		</table>
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Large Structures]]
	[[Category: Nalam, M N.L]]		[[Category: Nalam, M N.L]]
	[[Category: Schiffer, C A]]		[[Category: Schiffer, C A]]

OCA at 19:00, 24 January 2018

2018-01-24T19:00:09Z

←Older revision		Revision as of 19:00, 24 January 2018
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	Check<jmol>		Check<jmol>
	<jmolCheckbox>		<jmolCheckbox>
-	<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/qi/2qi3_consurf.spt"</scriptWhenChecked>	+	<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/qi/2qi3_consurf.spt"</scriptWhenChecked>
	<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>		<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
	<text>to colour the structure by Evolutionary Conservation</text>		<text>to colour the structure by Evolutionary Conservation</text>

OCA at 09:48, 18 October 2017

2017-10-18T09:48:46Z

←Older revision		Revision as of 09:48, 18 October 2017
Line 1:		Line 1:
		+
	==Crystal structure of protease inhibitor, MIT-2-AD94 in complex with wild type HIV-1 protease==		==Crystal structure of protease inhibitor, MIT-2-AD94 in complex with wild type HIV-1 protease==
	<StructureSection load='2qi3' size='340' side='right' caption='[[2qi3]], [[Resolution\|resolution]] 1.95Å' scene=''>		<StructureSection load='2qi3' size='340' side='right' caption='[[2qi3]], [[Resolution\|resolution]] 1.95Å' scene=''>
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	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2qhy\|2qhy]], [[2qhz\|2qhz]], [[2qi0\|2qi0]], [[2qi1\|2qi1]], [[2qi4\|2qi4]], [[2qi5\|2qi5]], [[2qi6\|2qi6]], [[2qi7\|2qi7]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2qhy\|2qhy]], [[2qhz\|2qhz]], [[2qi0\|2qi0]], [[2qi1\|2qi1]], [[2qi4\|2qi4]], [[2qi5\|2qi5]], [[2qi6\|2qi6]], [[2qi7\|2qi7]]</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=11676 9HIV1])</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=11676 9HIV1])</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=2qi3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2qi3 OCA], [http://pdbe.org/2qi3 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2qi3 RCSB], [http://www.ebi.ac.uk/pdbsum/2qi3 PDBsum]</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=2qi3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2qi3 OCA], [http://pdbe.org/2qi3 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2qi3 RCSB], [http://www.ebi.ac.uk/pdbsum/2qi3 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2qi3 ProSAT]</span></td></tr>
	</table>		</table>
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
Line 16:		Line 17:
	<text>to colour the structure by Evolutionary Conservation</text>		<text>to colour the structure by Evolutionary Conservation</text>
	</jmolCheckbox>		</jmolCheckbox>
-	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/~~chain_selection~~.php?pdb_ID=~~2ata~~ ConSurf].	+	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2qi3 ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">

OCA at 12:57, 11 September 2015

2015-09-11T12:57:54Z

←Older revision		Revision as of 12:57, 11 September 2015
Line 2:		Line 2:
	<StructureSection load='2qi3' size='340' side='right' caption='[[2qi3]], [[Resolution\|resolution]] 1.95Å' scene=''>		<StructureSection load='2qi3' size='340' side='right' caption='[[2qi3]], [[Resolution\|resolution]] 1.95Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[2qi3]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/~~Human_immunodeficiency_virus_1 Human immunodeficiency virus 1~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2QI3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2QI3 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[2qi3]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/9hiv1 9hiv1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2QI3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2QI3 FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MZ5:(2S)-N-[(1S,2R)-3-{(1,3-BENZOTHIAZOL-6-YLSULFONYL)[(2S)-2-METHYLBUTYL]AMINO}-1-BENZYL-2-HYDROXYPROPYL]-2-HYDROXY-3-METHYLBUTANAMIDE'>MZ5</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MZ5:(2S)-N-[(1S,2R)-3-{(1,3-BENZOTHIAZOL-6-YLSULFONYL)[(2S)-2-METHYLBUTYL]AMINO}-1-BENZYL-2-HYDROXYPROPYL]-2-HYDROXY-3-METHYLBUTANAMIDE'>MZ5</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2qhy\|2qhy]], [[2qhz\|2qhz]], [[2qi0\|2qi0]], [[2qi1\|2qi1]], [[2qi4\|2qi4]], [[2qi5\|2qi5]], [[2qi6\|2qi6]], [[2qi7\|2qi7]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2qhy\|2qhy]], [[2qhz\|2qhz]], [[2qi0\|2qi0]], [[2qi1\|2qi1]], [[2qi4\|2qi4]], [[2qi5\|2qi5]], [[2qi6\|2qi6]], [[2qi7\|2qi7]]</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=11676 ~~Human immunodeficiency virus 1~~])</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=11676 9HIV1])</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=2qi3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2qi3 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2qi3 RCSB], [http://www.ebi.ac.uk/pdbsum/2qi3 PDBsum]</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=2qi3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2qi3 OCA], [http://pdbe.org/2qi3 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2qi3 RCSB], [http://www.ebi.ac.uk/pdbsum/2qi3 PDBsum]</span></td></tr>
	</table>		</table>
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
Line 26:		Line 26:
	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	</div>		</div>
		+	<div class="pdbe-citations 2qi3" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: Human immunodeficiency virus 1]]
	[[Category: Nalam, M N.L]]		[[Category: Nalam, M N.L]]
	[[Category: Schiffer, C A]]		[[Category: Schiffer, C A]]

OCA at 17:46, 19 January 2015

2015-01-19T17:46:22Z

←Older revision		Revision as of 17:46, 19 January 2015
Line 3:		Line 3:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[2qi3]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human_immunodeficiency_virus_1 Human immunodeficiency virus 1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2QI3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2QI3 FirstGlance]. <br>		<table><tr><td colspan='2'>[[2qi3]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human_immunodeficiency_virus_1 Human immunodeficiency virus 1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2QI3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2QI3 FirstGlance]. <br>
-	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MZ5:(2S)-N-[(1S,2R)-3-{(1,3-BENZOTHIAZOL-6-YLSULFONYL)[(2S)-2-METHYLBUTYL]AMINO}-1-BENZYL-2-HYDROXYPROPYL]-2-HYDROXY-3-METHYLBUTANAMIDE'>MZ5</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene><br>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MZ5:(2S)-N-[(1S,2R)-3-{(1,3-BENZOTHIAZOL-6-YLSULFONYL)[(2S)-2-METHYLBUTYL]AMINO}-1-BENZYL-2-HYDROXYPROPYL]-2-HYDROXY-3-METHYLBUTANAMIDE'>MZ5</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr>
-	<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2qhy\|2qhy]], [[2qhz\|2qhz]], [[2qi0\|2qi0]], [[2qi1\|2qi1]], [[2qi4\|2qi4]], [[2qi5\|2qi5]], [[2qi6\|2qi6]], [[2qi7\|2qi7]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2qhy\|2qhy]], [[2qhz\|2qhz]], [[2qi0\|2qi0]], [[2qi1\|2qi1]], [[2qi4\|2qi4]], [[2qi5\|2qi5]], [[2qi6\|2qi6]], [[2qi7\|2qi7]]</td></tr>
-	<tr><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=11676 Human immunodeficiency virus 1])</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=11676 Human immunodeficiency virus 1])</td></tr>
-	<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2qi3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2qi3 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2qi3 RCSB], [http://www.ebi.ac.uk/pdbsum/2qi3 PDBsum]</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=2qi3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2qi3 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2qi3 RCSB], [http://www.ebi.ac.uk/pdbsum/2qi3 PDBsum]</span></td></tr>
-	<table>	+	</table>
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
Line 32:		Line 32:
	[[Category: Human immunodeficiency virus 1]]		[[Category: Human immunodeficiency virus 1]]
	[[Category: Nalam, M N.L]]		[[Category: Nalam, M N.L]]
-	[[Category: Schiffer, C A.]]	+	[[Category: Schiffer, C A]]
	[[Category: Drug design]]		[[Category: Drug design]]
	[[Category: Hiv-1 protease]]		[[Category: Hiv-1 protease]]
	[[Category: Hydrolase]]		[[Category: Hydrolase]]
	[[Category: Protease inhibitor]]		[[Category: Protease inhibitor]]

OCA at 20:03, 30 September 2014

2014-09-30T20:03:42Z

←Older revision		Revision as of 20:03, 30 September 2014
Line 1:		Line 1:
-	[[~~Image:~~2qi3.~~png~~\|~~left~~\|200px]]	+	==Crystal structure of protease inhibitor, MIT-2-AD94 in complex with wild type HIV-1 protease==
		+	<StructureSection load='2qi3' size='340' side='right' caption='[[2qi3]], [[Resolution\|resolution]] 1.95Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[2qi3]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human_immunodeficiency_virus_1 Human immunodeficiency virus 1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2QI3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2QI3 FirstGlance]. <br>
		+	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MZ5:(2S)-N-[(1S,2R)-3-{(1,3-BENZOTHIAZOL-6-YLSULFONYL)[(2S)-2-METHYLBUTYL]AMINO}-1-BENZYL-2-HYDROXYPROPYL]-2-HYDROXY-3-METHYLBUTANAMIDE'>MZ5</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene><br>
		+	<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2qhy\|2qhy]], [[2qhz\|2qhz]], [[2qi0\|2qi0]], [[2qi1\|2qi1]], [[2qi4\|2qi4]], [[2qi5\|2qi5]], [[2qi6\|2qi6]], [[2qi7\|2qi7]]</td></tr>
		+	<tr><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=11676 Human immunodeficiency virus 1])</td></tr>
		+	<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2qi3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2qi3 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2qi3 RCSB], [http://www.ebi.ac.uk/pdbsum/2qi3 PDBsum]</span></td></tr>
		+	<table>
		+	== Evolutionary Conservation ==
		+	[[Image:Consurf_key_small.gif\|200px\|right]]
		+	Check<jmol>
		+	<jmolCheckbox>
		+	<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/qi/2qi3_consurf.spt"</scriptWhenChecked>
		+	<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
		+	<text>to colour the structure by Evolutionary Conservation</text>
		+	</jmolCheckbox>
		+	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf].
		+	<div style="clear:both"></div>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The acquisition of drug-resistant mutations by infectious pathogens remains a pressing health concern, and the development of strategies to combat this threat is a priority. Here we have applied a general strategy, inverse design using the substrate envelope, to develop inhibitors of HIV-1 protease. Structure-based computation was used to design inhibitors predicted to stay within a consensus substrate volume in the binding site. Two rounds of design, synthesis, experimental testing, and structural analysis were carried out, resulting in a total of 51 compounds. Improvements in design methodology led to a roughly 1000-fold affinity enhancement to a wild-type protease for the best binders, from a Ki of 30-50 nM in round one to below 100 pM in round two. Crystal structures of a subset of complexes revealed a binding mode similar to each design that respected the substrate envelope in nearly all cases. All four best binders from round one exhibited broad specificity against a clinically relevant panel of drug-resistant HIV-1 protease variants, losing no more than 6-13-fold affinity relative to wild type. Testing a subset of second-round compounds against the panel of resistant variants revealed three classes of inhibitors: robust binders (maximum affinity loss of 14-16-fold), moderate binders (35-80-fold), and susceptible binders (greater than 100-fold). Although for especially high-affinity inhibitors additional factors may also be important, overall, these results suggest that designing inhibitors using the substrate envelope may be a useful strategy in the development of therapeutics with low susceptibility to resistance.

-	~~{{STRUCTURE_2qi3\| PDB=2qi3 \| SCENE= }}~~	+	HIV-1 protease inhibitors from inverse design in the substrate envelope exhibit subnanomolar binding to drug-resistant variants.,Altman MD, Ali A, Reddy GS, Nalam MN, Anjum SG, Cao H, Chellappan S, Kairys V, Fernandes MX, Gilson MK, Schiffer CA, Rana TM, Tidor B J Am Chem Soc. 2008 May 14;130(19):6099-113. Epub 2008 Apr 16. PMID:18412349<ref>PMID:18412349</ref>

-	~~===Crystal structure of protease inhibitor~~, ~~MIT-2-AD94 in complex with wild type HIV-1 protease===~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-		+	</div>
-	~~{{ABSTRACT_PUBMED_18412349}}~~	+	== References ==
-		+	<references/>
-	~~==About this Structure==~~	+	__TOC__
-	~~[[2qi3]] is~~ a ~~2 chain structure with sequence from [http://en~~.~~wikipedia~~.~~org/wiki/Human_immunodeficiency_virus_1 Human immunodeficiency virus 1]~~. ~~Full crystallographic information is available from [http:~~/~~/oca.weizmann.ac.il/oca-bin/ocashort?id=2QI3 OCA].~~	+	</StructureSection>
-		+
-	==~~Reference~~==	+
-	<~~ref group="xtra">PMID:018412349<~~/~~ref~~><~~references group="xtra"~~/>	+
	[[Category: Human immunodeficiency virus 1]]		[[Category: Human immunodeficiency virus 1]]
	[[Category: Nalam, M N.L]]		[[Category: Nalam, M N.L]]

OCA: Protected "2qi3" [edit=sysop:move=sysop]

2013-01-07T20:09:06Z

Protected "2qi3" [edit=sysop:move=sysop]

←Older revision

Revision as of 20:09, 7 January 2013

OCA at 20:09, 7 January 2013

2013-01-07T20:09:01Z

←Older revision		Revision as of 20:09, 7 January 2013
Line 1:		Line 1:
-	{{Seed}}
	[[Image:2qi3.png\|left\|200px]]		[[Image:2qi3.png\|left\|200px]]

-	<!--
-	The line below this paragraph, containing "STRUCTURE_2qi3", creates the "Structure Box" on the page.
-	You may change the PDB parameter (which sets the PDB file loaded into the applet)
-	or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-	or leave the SCENE parameter empty for the default display.
-	-->
	{{STRUCTURE_2qi3\| PDB=2qi3 \| SCENE= }}		{{STRUCTURE_2qi3\| PDB=2qi3 \| SCENE= }}

	===Crystal structure of protease inhibitor, MIT-2-AD94 in complex with wild type HIV-1 protease===		===Crystal structure of protease inhibitor, MIT-2-AD94 in complex with wild type HIV-1 protease===

-
-	<!--
-	The line below this paragraph, {{ABSTRACT_PUBMED_18412349}}, adds the Publication Abstract to the page
-	(as it appears on PubMed at http://www.pubmed.gov), where 18412349 is the PubMed ID number.
-	-->
	{{ABSTRACT_PUBMED_18412349}}		{{ABSTRACT_PUBMED_18412349}}

	==About this Structure==		==About this Structure==
-	~~2QI3~~ is a 2 ~~chains~~ structure ~~of sequences~~ from [http://en.wikipedia.org/wiki/Human_immunodeficiency_virus_1 Human immunodeficiency virus 1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2QI3 OCA].	+	[[2qi3]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human_immunodeficiency_virus_1 Human immunodeficiency virus 1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2QI3 OCA].

	==Reference==		==Reference==
-	<ref group="xtra">PMID:~~18412349~~</ref><references group="xtra"/>	+	<ref group="xtra">PMID:018412349</ref><references group="xtra"/>
	[[Category: Human immunodeficiency virus 1]]		[[Category: Human immunodeficiency virus 1]]
	[[Category: Nalam, M N.L]]		[[Category: Nalam, M N.L]]
Line 31:		Line 19:
	[[Category: Hydrolase]]		[[Category: Hydrolase]]
	[[Category: Protease inhibitor]]		[[Category: Protease inhibitor]]
-
-	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Feb 17 22:07:58 2009''

OCA at 20:07, 17 February 2009

2009-02-17T20:07:59Z

←Older revision		Revision as of 20:07, 17 February 2009
Line 20:		Line 20:

	==About this Structure==		==About this Structure==
-	2QI3 is a ~~[[Single protein]]~~ structure of ~~sequence~~ from [http://en.wikipedia.org/wiki/Human_immunodeficiency_virus_1 Human immunodeficiency virus 1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2QI3 OCA].	+	2QI3 is a 2 chains structure of sequences from [http://en.wikipedia.org/wiki/Human_immunodeficiency_virus_1 Human immunodeficiency virus 1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2QI3 OCA].

	==Reference==		==Reference==
-	HIV-1 protease inhibitors from inverse design in the substrate envelope exhibit subnanomolar binding to drug-resistant variants., Altman MD, Ali A, Reddy GS, Nalam MN, Anjum SG, Cao H, Chellappan S, Kairys V, Fernandes MX, Gilson MK, Schiffer CA, Rana TM, Tidor B, J Am Chem Soc. 2008 May 14;130(19):6099-113. Epub 2008 Apr 16. PMID:~~[http:~~//~~www.ncbi.nlm.nih.gov/pubmed/18412349 18412349]~~	+	<ref group="xtra">PMID:18412349</ref><references group="xtra"/>
	[[Category: Human immunodeficiency virus 1]]		[[Category: Human immunodeficiency virus 1]]
-	[[Category: Single protein]]
	[[Category: Nalam, M N.L]]		[[Category: Nalam, M N.L]]
	[[Category: Schiffer, C A.]]		[[Category: Schiffer, C A.]]
Line 33:		Line 32:
	[[Category: Protease inhibitor]]		[[Category: Protease inhibitor]]

-	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue ~~Jul 29 06:~~22:~~52 2008~~''	+	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Feb 17 22:07:58 2009''