4dv8 - Revision history

OCA at 11:00, 1 March 2024

2024-03-01T11:00:22Z

←Older revision		Revision as of 11:00, 1 March 2024
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4dv8]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Bacillus_anthracis Bacillus anthracis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4DV8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4DV8 FirstGlance]. <br>		<table><tr><td colspan='2'>[[4dv8]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Bacillus_anthracis Bacillus anthracis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4DV8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4DV8 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0LX:(2S)-6-[(4-FLUOROBENZYL)AMINO]-2-[(2R)-2-(4-FLUOROPHENYL)-2-METHOXYETHYL]-N-HYDROXYHEXANAMIDE'>0LX</scene>, <scene name='pdbligand=MLI:MALONATE+ION'>MLI</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]] 1.632Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0LX:(2S)-6-[(4-FLUOROBENZYL)AMINO]-2-[(2R)-2-(4-FLUOROPHENYL)-2-METHOXYETHYL]-N-HYDROXYHEXANAMIDE'>0LX</scene>, <scene name='pdbligand=MLI:MALONATE+ION'>MLI</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'>[https://proteopedia.org/fgij/fg.htm?mol=4dv8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4dv8 OCA], [https://pdbe.org/4dv8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4dv8 RCSB], [https://www.ebi.ac.uk/pdbsum/4dv8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4dv8 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=4dv8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4dv8 OCA], [https://pdbe.org/4dv8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4dv8 RCSB], [https://www.ebi.ac.uk/pdbsum/4dv8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4dv8 ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[https://www.uniprot.org/uniprot/LEF_BACAN LEF_BACAN]] One of the three proteins composing the anthrax toxin, the agent which infects many mammalian species and that may cause death. LF is the lethal factor that, when associated with PA, causes death. LF is not toxic by itself. It is a protease that cleaves the N-terminal of most dual specificity mitogen-activated protein kinase kinases (MAPKKs or MAP2Ks) (except for MAP2K5). Cleavage invariably occurs within the N-terminal proline-rich region preceding the kinase domain, thus disrupting a sequence involved in directing specific protein-protein interactions necessary for the assembly of signaling complexes. There may be other cytosolic targets of LF involved in cytotoxicity. The proteasome may mediate a toxic process initiated by LF in the cell cytosol involving degradation of unidentified molecules that are essential for macrophage homeostasis. This is an early step in LeTx intoxication, but it is downstream of the cleavage by LF of MEK1 or other putative substrates.<ref>PMID:9563949</ref> <ref>PMID:9703991</ref> <ref>PMID:10475971</ref> <ref>PMID:11104681</ref> <ref>PMID:10338520</ref>	+	[https://www.uniprot.org/uniprot/LEF_BACAN LEF_BACAN] One of the three proteins composing the anthrax toxin, the agent which infects many mammalian species and that may cause death. LF is the lethal factor that, when associated with PA, causes death. LF is not toxic by itself. It is a protease that cleaves the N-terminal of most dual specificity mitogen-activated protein kinase kinases (MAPKKs or MAP2Ks) (except for MAP2K5). Cleavage invariably occurs within the N-terminal proline-rich region preceding the kinase domain, thus disrupting a sequence involved in directing specific protein-protein interactions necessary for the assembly of signaling complexes. There may be other cytosolic targets of LF involved in cytotoxicity. The proteasome may mediate a toxic process initiated by LF in the cell cytosol involving degradation of unidentified molecules that are essential for macrophage homeostasis. This is an early step in LeTx intoxication, but it is downstream of the cleavage by LF of MEK1 or other putative substrates.<ref>PMID:9563949</ref> <ref>PMID:9703991</ref> <ref>PMID:10475971</ref> <ref>PMID:11104681</ref> <ref>PMID:10338520</ref>
-	~~<div style="background-color:#fffaf0;">~~	+
-	~~== Publication Abstract from PubMed ==~~	+
-	Four core structures capable of providing sub-nanomolar inhibitors of anthrax lethal factor (LF) were evaluated by comparing the potential for toxicity, physicochemical properties, in vitro ADME profiles, and relative efficacy in a rat lethal toxin (LT) model of LF intoxication. Poor efficacy in the rat LT model exhibited by the phenoxyacetic acid series (3) correlated with low rat microsome and plasma stability. Specific molecular interactions contributing to the high affinity of inhibitors with a secondary amine in the C2-side chain were revealed by X-ray crystallography.	+
-		+
-	Antidotes to anthrax lethal factor intoxication. Part 3: Evaluation of core structures and further modifications to the C2-side chain.,Jiao GS, Kim S, Moayeri M, Crown D, Thai A, Cregar-Hernandez L, McKasson L, Sankaran B, Lehrer A, Wong T, Johns L, Margosiak SA, Leppla SH, Johnson AT Bioorg Med Chem Lett. 2012 Mar 15;22(6):2242-6. Epub 2012 Feb 1. PMID:22342144<ref>PMID:22342144</ref>	+
-		+
-	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~	+
-	~~</div>~~	+
-	~~<div class="pdbe-citations 4dv8" style="background-color:#fffaf0;"></div~~>	+

	==See Also==		==See Also==

OCA at 08:40, 21 September 2022

2022-09-21T08:40:02Z

←Older revision		Revision as of 08:40, 21 September 2022
Line 1:		Line 1:

	==Anthrax Lethal Factor metalloproteinase in complex with the Hydroxamic acid based small molecule PT8421==		==Anthrax Lethal Factor metalloproteinase in complex with the Hydroxamic acid based small molecule PT8421==
-	<StructureSection load='4dv8' size='340' side='right' caption='[[4dv8]], [[Resolution\|resolution]] 1.63Å' scene=''>	+	<StructureSection load='4dv8' size='340' side='right'caption='[[4dv8]], [[Resolution\|resolution]] 1.63Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4dv8]] is a 1 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~"bacillus_cereus_var._anthracis"_(cohn_1872)_smith_et_al._1946 "bacillus cereus var.~~ anthracis~~" (cohn 1872) smith et al. 1946~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4DV8 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4DV8 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4dv8]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Bacillus_anthracis Bacillus anthracis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4DV8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4DV8 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0LX:(2S)-6-[(4-FLUOROBENZYL)AMINO]-2-[(2R)-2-(4-FLUOROPHENYL)-2-METHOXYETHYL]-N-HYDROXYHEXANAMIDE'>0LX</scene>, <scene name='pdbligand=MLI:MALONATE+ION'>MLI</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=0LX:(2S)-6-[(4-FLUOROBENZYL)AMINO]-2-[(2R)-2-(4-FLUOROPHENYL)-2-METHOXYETHYL]-N-HYDROXYHEXANAMIDE'>0LX</scene>, <scene name='pdbligand=MLI:MALONATE+ION'>MLI</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">lef, pXO1-107, BXA0172, GBAA_pXO1_0172 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1392 "Bacillus cereus var. anthracis" (Cohn 1872) Smith et al. 1946])</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=4dv8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4dv8 OCA], [https://pdbe.org/4dv8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4dv8 RCSB], [https://www.ebi.ac.uk/pdbsum/4dv8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4dv8 ProSAT]</span></td></tr>
-	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Hydrolase Hydrolase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.24.83 3.4.24.83] </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=4dv8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4dv8 OCA], [~~http~~://pdbe.org/4dv8 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4dv8 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4dv8 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4dv8 ProSAT]</span></td></tr>	+
	</table>		</table>
	== Function ==		== Function ==
-	[[~~http~~://www.uniprot.org/uniprot/LEF_BACAN LEF_BACAN]] One of the three proteins composing the anthrax toxin, the agent which infects many mammalian species and that may cause death. LF is the lethal factor that, when associated with PA, causes death. LF is not toxic by itself. It is a protease that cleaves the N-terminal of most dual specificity mitogen-activated protein kinase kinases (MAPKKs or MAP2Ks) (except for MAP2K5). Cleavage invariably occurs within the N-terminal proline-rich region preceding the kinase domain, thus disrupting a sequence involved in directing specific protein-protein interactions necessary for the assembly of signaling complexes. There may be other cytosolic targets of LF involved in cytotoxicity. The proteasome may mediate a toxic process initiated by LF in the cell cytosol involving degradation of unidentified molecules that are essential for macrophage homeostasis. This is an early step in LeTx intoxication, but it is downstream of the cleavage by LF of MEK1 or other putative substrates.<ref>PMID:9563949</ref> <ref>PMID:9703991</ref> <ref>PMID:10475971</ref> <ref>PMID:11104681</ref> <ref>PMID:10338520</ref>	+	[[https://www.uniprot.org/uniprot/LEF_BACAN LEF_BACAN]] One of the three proteins composing the anthrax toxin, the agent which infects many mammalian species and that may cause death. LF is the lethal factor that, when associated with PA, causes death. LF is not toxic by itself. It is a protease that cleaves the N-terminal of most dual specificity mitogen-activated protein kinase kinases (MAPKKs or MAP2Ks) (except for MAP2K5). Cleavage invariably occurs within the N-terminal proline-rich region preceding the kinase domain, thus disrupting a sequence involved in directing specific protein-protein interactions necessary for the assembly of signaling complexes. There may be other cytosolic targets of LF involved in cytotoxicity. The proteasome may mediate a toxic process initiated by LF in the cell cytosol involving degradation of unidentified molecules that are essential for macrophage homeostasis. This is an early step in LeTx intoxication, but it is downstream of the cleavage by LF of MEK1 or other putative substrates.<ref>PMID:9563949</ref> <ref>PMID:9703991</ref> <ref>PMID:10475971</ref> <ref>PMID:11104681</ref> <ref>PMID:10338520</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 20:		Line 18:
	</div>		</div>
	<div class="pdbe-citations 4dv8" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 4dv8" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Anthrax lethal factor 3D structures\|Anthrax lethal factor 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Hydrolase~~]]	+	[[Category: Bacillus anthracis]]
-	[[Category: ~~Margosiak, S A~~]]	+	[[Category: Large Structures]]
-	[[Category: ~~Sankaran, B~~]]	+	[[Category: Margosiak SA]]
-	[[Category: ~~Endopeptidase]]~~	+	[[Category: Sankaran B]]
-	~~[[Category: Zinc dependent~~]]	+

OCA at 07:57, 15 November 2017

2017-11-15T07:57:13Z

←Older revision		Revision as of 07:57, 15 November 2017
Line 20:		Line 20:
	</div>		</div>
	<div class="pdbe-citations 4dv8" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 4dv8" style="background-color:#fffaf0;"></div>
-
-	==See Also==
-	*[[Anthrax Lethal Factor\|Anthrax Lethal Factor]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 23:01, 5 August 2016

2016-08-05T23:01:20Z

←Older revision		Revision as of 23:01, 5 August 2016
Line 1:		Line 1:
		+
	==Anthrax Lethal Factor metalloproteinase in complex with the Hydroxamic acid based small molecule PT8421==		==Anthrax Lethal Factor metalloproteinase in complex with the Hydroxamic acid based small molecule PT8421==
	<StructureSection load='4dv8' size='340' side='right' caption='[[4dv8]], [[Resolution\|resolution]] 1.63Å' scene=''>		<StructureSection load='4dv8' size='340' side='right' caption='[[4dv8]], [[Resolution\|resolution]] 1.63Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4dv8]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/~~Bacillus_anthracis Bacillus~~ anthracis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4DV8 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4DV8 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4dv8]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_cereus_var._anthracis"_(cohn_1872)_smith_et_al._1946 "bacillus cereus var. anthracis" (cohn 1872) smith et al. 1946]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4DV8 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4DV8 FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0LX:(2S)-6-[(4-FLUOROBENZYL)AMINO]-2-[(2R)-2-(4-FLUOROPHENYL)-2-METHOXYETHYL]-N-HYDROXYHEXANAMIDE'>0LX</scene>, <scene name='pdbligand=MLI:MALONATE+ION'>MLI</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=0LX:(2S)-6-[(4-FLUOROBENZYL)AMINO]-2-[(2R)-2-(4-FLUOROPHENYL)-2-METHOXYETHYL]-N-HYDROXYHEXANAMIDE'>0LX</scene>, <scene name='pdbligand=MLI:MALONATE+ION'>MLI</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">lef, pXO1-107, BXA0172, GBAA_pXO1_0172 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1392 Bacillus anthracis])</td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">lef, pXO1-107, BXA0172, GBAA_pXO1_0172 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1392 "Bacillus cereus var. anthracis" (Cohn 1872) Smith et al. 1946])</td></tr>
-	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/~~Anthrax_lethal_factor_endopeptidase Anthrax lethal factor endopeptidase~~], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.24.83 3.4.24.83] </span></td></tr>	+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Hydrolase Hydrolase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.24.83 3.4.24.83] </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=4dv8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4dv8 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4dv8 RCSB], [http://www.ebi.ac.uk/pdbsum/4dv8 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=4dv8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4dv8 OCA], [http://pdbe.org/4dv8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4dv8 RCSB], [http://www.ebi.ac.uk/pdbsum/4dv8 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4dv8 ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 18:		Line 19:
	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 4dv8" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 25:		Line 27:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Anthrax lethal factor endopeptidase]]~~	+	[[Category: Hydrolase]]
-	~~[[Category: Bacillus anthracis~~]]	+
	[[Category: Margosiak, S A]]		[[Category: Margosiak, S A]]
	[[Category: Sankaran, B]]		[[Category: Sankaran, B]]
	[[Category: Endopeptidase]]		[[Category: Endopeptidase]]
-	[[Category: Hydrolase]]
	[[Category: Zinc dependent]]		[[Category: Zinc dependent]]

OCA at 22:41, 25 December 2014

2014-12-25T22:41:15Z

←Older revision		Revision as of 22:41, 25 December 2014
Line 3:		Line 3:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4dv8]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Bacillus_anthracis Bacillus anthracis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4DV8 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4DV8 FirstGlance]. <br>		<table><tr><td colspan='2'>[[4dv8]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Bacillus_anthracis Bacillus anthracis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4DV8 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4DV8 FirstGlance]. <br>
-	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0LX:(2S)-6-[(4-FLUOROBENZYL)AMINO]-2-[(2R)-2-(4-FLUOROPHENYL)-2-METHOXYETHYL]-N-HYDROXYHEXANAMIDE'>0LX</scene>, <scene name='pdbligand=MLI:MALONATE+ION'>MLI</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene><br>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0LX:(2S)-6-[(4-FLUOROBENZYL)AMINO]-2-[(2R)-2-(4-FLUOROPHENYL)-2-METHOXYETHYL]-N-HYDROXYHEXANAMIDE'>0LX</scene>, <scene name='pdbligand=MLI:MALONATE+ION'>MLI</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
-	<tr><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">lef, pXO1-107, BXA0172, GBAA_pXO1_0172 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1392 Bacillus anthracis])</td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">lef, pXO1-107, BXA0172, GBAA_pXO1_0172 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1392 Bacillus anthracis])</td></tr>
-	<tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Anthrax_lethal_factor_endopeptidase Anthrax lethal factor endopeptidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.24.83 3.4.24.83] </span></td></tr>	+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Anthrax_lethal_factor_endopeptidase Anthrax lethal factor endopeptidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.24.83 3.4.24.83] </span></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=4dv8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4dv8 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4dv8 RCSB], [http://www.ebi.ac.uk/pdbsum/4dv8 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=4dv8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4dv8 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4dv8 RCSB], [http://www.ebi.ac.uk/pdbsum/4dv8 PDBsum]</span></td></tr>
-	<table>	+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/LEF_BACAN LEF_BACAN]] One of the three proteins composing the anthrax toxin, the agent which infects many mammalian species and that may cause death. LF is the lethal factor that, when associated with PA, causes death. LF is not toxic by itself. It is a protease that cleaves the N-terminal of most dual specificity mitogen-activated protein kinase kinases (MAPKKs or MAP2Ks) (except for MAP2K5). Cleavage invariably occurs within the N-terminal proline-rich region preceding the kinase domain, thus disrupting a sequence involved in directing specific protein-protein interactions necessary for the assembly of signaling complexes. There may be other cytosolic targets of LF involved in cytotoxicity. The proteasome may mediate a toxic process initiated by LF in the cell cytosol involving degradation of unidentified molecules that are essential for macrophage homeostasis. This is an early step in LeTx intoxication, but it is downstream of the cleavage by LF of MEK1 or other putative substrates.<ref>PMID:9563949</ref> <ref>PMID:9703991</ref> <ref>PMID:10475971</ref> <ref>PMID:11104681</ref> <ref>PMID:10338520</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 25:		Line 27:
	[[Category: Anthrax lethal factor endopeptidase]]		[[Category: Anthrax lethal factor endopeptidase]]
	[[Category: Bacillus anthracis]]		[[Category: Bacillus anthracis]]
-	[[Category: Margosiak, S A.]]	+	[[Category: Margosiak, S A]]
-	[[Category: Sankaran, B.]]	+	[[Category: Sankaran, B]]
	[[Category: Endopeptidase]]		[[Category: Endopeptidase]]
	[[Category: Hydrolase]]		[[Category: Hydrolase]]
	[[Category: Zinc dependent]]		[[Category: Zinc dependent]]

OCA at 08:02, 5 June 2014

2014-06-05T08:02:30Z

←Older revision		Revision as of 08:02, 5 June 2014
Line 1:		Line 1:
-	[[~~Image:~~4dv8.~~jpg~~\|~~left~~\|~~200px~~]]	+	==Anthrax Lethal Factor metalloproteinase in complex with the Hydroxamic acid based small molecule PT8421==
		+	<StructureSection load='4dv8' size='340' side='right' caption='[[4dv8]], [[Resolution\|resolution]] 1.63Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[4dv8]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Bacillus_anthracis Bacillus anthracis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4DV8 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4DV8 FirstGlance]. <br>
		+	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0LX:(2S)-6-[(4-FLUOROBENZYL)AMINO]-2-[(2R)-2-(4-FLUOROPHENYL)-2-METHOXYETHYL]-N-HYDROXYHEXANAMIDE'>0LX</scene>, <scene name='pdbligand=MLI:MALONATE+ION'>MLI</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene><br>
		+	<tr><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">lef, pXO1-107, BXA0172, GBAA_pXO1_0172 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1392 Bacillus anthracis])</td></tr>
		+	<tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Anthrax_lethal_factor_endopeptidase Anthrax lethal factor endopeptidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.24.83 3.4.24.83] </span></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=4dv8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4dv8 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4dv8 RCSB], [http://www.ebi.ac.uk/pdbsum/4dv8 PDBsum]</span></td></tr>
		+	<table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Four core structures capable of providing sub-nanomolar inhibitors of anthrax lethal factor (LF) were evaluated by comparing the potential for toxicity, physicochemical properties, in vitro ADME profiles, and relative efficacy in a rat lethal toxin (LT) model of LF intoxication. Poor efficacy in the rat LT model exhibited by the phenoxyacetic acid series (3) correlated with low rat microsome and plasma stability. Specific molecular interactions contributing to the high affinity of inhibitors with a secondary amine in the C2-side chain were revealed by X-ray crystallography.

-	<!--	+	Antidotes to anthrax lethal factor intoxication. Part 3: Evaluation of core structures and further modifications to the C2-side chain.,Jiao GS, Kim S, Moayeri M, Crown D, Thai A, Cregar-Hernandez L, McKasson L, Sankaran B, Lehrer A, Wong T, Johns L, Margosiak SA, Leppla SH, Johnson AT Bioorg Med Chem Lett. 2012 Mar 15;22(6):2242-6. Epub 2012 Feb 1. PMID:22342144<ref>PMID:22342144</ref>
-	~~The line below this paragraph~~, ~~containing "STRUCTURE_4dv8"~~, ~~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_4dv8\| PDB=4dv8 \| SCENE= }}~~	+

-	~~===Anthrax Lethal Factor metalloproteinase in complex with~~ the ~~Hydroxamic acid based small molecule PT8421===~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>

-		+	==See Also==
-	~~<!--~~	+	*[[Anthrax Lethal Factor\|Anthrax Lethal Factor]]
-	~~The line below this paragraph, {{ABSTRACT_PUBMED_22342144}}, adds the Publication Abstract to the page~~	+	== References ==
-	~~(as it appears on PubMed at http://www.pubmed.gov), where 22342144 is the PubMed ID number.~~	+	<references/>
-	~~-->~~	+	__TOC__
-	~~{{ABSTRACT_PUBMED_22342144}}~~	+	</StructureSection>
-		+
-	==~~About this Structure~~==	+
-	[[~~4dv8~~]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Bacillus_anthracis Bacillus anthracis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4DV8 OCA].	+
-		+
-	==~~Reference~~==	+
-	<~~ref group="xtra">PMID:022342144<~~/~~ref~~><~~references group="xtra"~~/>	+
	[[Category: Anthrax lethal factor endopeptidase]]		[[Category: Anthrax lethal factor endopeptidase]]
	[[Category: Bacillus anthracis]]		[[Category: Bacillus anthracis]]

OCA at 06:33, 14 March 2012

2012-03-14T06:33:24Z

←Older revision		Revision as of 06:33, 14 March 2012
Line 1:		Line 1:
-	~~'''Unreleased structure'''~~	+	[[Image:4dv8.jpg\|left\|200px]]

-	The ~~entry 4dv8~~ is ~~ON HOLD~~	+	<!--
		+	The line below this paragraph, containing "STRUCTURE_4dv8", 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_4dv8\| PDB=4dv8 \| SCENE= }}

-	~~Authors: Margosiak, S.A., Sankaran, B.~~	+	===Anthrax Lethal Factor metalloproteinase in complex with the Hydroxamic acid based small molecule PT8421===

-	~~Description~~: ~~Anthrax Lethal Factor metalloproteinase in complex with~~ the ~~Hydroxamic acid based small molecule PT8421~~	+
		+	<!--
		+	The line below this paragraph, {{ABSTRACT_PUBMED_22342144}}, adds the Publication Abstract to the page
		+	(as it appears on PubMed at http://www.pubmed.gov), where 22342144 is the PubMed ID number.
		+	-->
		+	{{ABSTRACT_PUBMED_22342144}}
		+
		+	==About this Structure==
		+	[[4dv8]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Bacillus_anthracis Bacillus anthracis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4DV8 OCA].
		+
		+	==Reference==
		+	<ref group="xtra">PMID:022342144</ref><references group="xtra"/>
		+	[[Category: Anthrax lethal factor endopeptidase]]
		+	[[Category: Bacillus anthracis]]
		+	[[Category: Margosiak, S A.]]
		+	[[Category: Sankaran, B.]]
		+	[[Category: Endopeptidase]]
		+	[[Category: Hydrolase]]
		+	[[Category: Zinc dependent]]

OCA: Protected "4dv8" [edit=sysop:move=sysop]

2012-02-29T08:29:30Z

Protected "4dv8" [edit=sysop:move=sysop]

←Older revision

Revision as of 08:29, 29 February 2012

OCA: New page: '''Unreleased structure''' The entry 4dv8 is ON HOLD Authors: Margosiak, S.A., Sankaran, B. Description: Anthrax Lethal Factor metalloproteinase in complex with the Hydroxamic acid bas...

2012-02-29T08:29:27Z

New page: '''Unreleased structure''' The entry 4dv8 is ON HOLD Authors: Margosiak, S.A., Sankaran, B. Description: Anthrax Lethal Factor metalloproteinase in complex with the Hydroxamic acid bas...

New page

'''Unreleased structure'''

The entry 4dv8 is ON HOLD

Authors: Margosiak, S.A., Sankaran, B.

Description: Anthrax Lethal Factor metalloproteinase in complex with the Hydroxamic acid based small molecule PT8421