6upo - Revision history

OCA at 07:56, 11 October 2023

2023-10-11T07:56:05Z

←Older revision		Revision as of 07:56, 11 October 2023
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	<StructureSection load='6upo' size='340' side='right'caption='[[6upo]], [[Resolution\|resolution]] 3.11Å' scene=''>		<StructureSection load='6upo' size='340' side='right'caption='[[6upo]], [[Resolution\|resolution]] 3.11Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6upo]] is a 2 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~Leishmania_major_mhom/il/81/friedlin~~ Leishmania major ~~mhom/il/81/friedlin~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6UPO OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6UPO FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6upo]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Leishmania_major_strain_Friedlin Leishmania major strain Friedlin]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6UPO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6UPO FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat"~~><scene name='pdbligand=LMR:(2S)-2-HYDROXYBUTANEDIOIC+ACID'>LMR</scene>, <scene name='pdbligand=SF4:IRON/SULFUR+CLUSTER'>SF4</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]] 3.113Å</td></tr>
-	~~<tr~~ id~~='related'><td class~~="~~sblockLbl~~">~~<b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[6unz\|6unz]]~~, [[~~6uo0~~\|~~6uo0]], [[6uoi\|6uoi]], [[6uoj\|6uoj]], [[6up9\|6up9]], [[6upm\|6upm]], [[6uq8\|6uq8]], [[6uq9\|6uq9]], [[6uqb\|6uqb]], [[6uql\|6uql]], [[6uqm\|6uqm]], [[6uqn\|6uqn~~]]</td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=LMR:(2S)-2-HYDROXYBUTANEDIOIC+ACID'>LMR</scene>, <scene name='pdbligand=SF4:IRON/SULFUR+CLUSTER'>SF4</scene></td></tr>
-	<tr id='~~gene~~'><td class="sblockLbl"><b>[[~~Gene~~\|~~Gene~~:]]</b></td><td class="sblockDat"~~>FH2, LMJF_29_1960 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&~~id=~~347515 Leishmania major MHOM/IL/81/Friedlin])</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=6upo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6upo OCA], [https://pdbe.org/6upo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6upo RCSB], [https://www.ebi.ac.uk/pdbsum/6upo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6upo 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/Fumarate_hydratase Fumarate hydratase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.2.1.2 4.2.1.2]~~ </~~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=6upo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6upo OCA], [~~http~~://pdbe.org/6upo PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6upo RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6upo PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6upo ProSAT]</span></td></tr>	+
	</table>		</table>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/FUM2_LEIMA FUM2_LEIMA]
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
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	</div>		</div>
	<div class="pdbe-citations 6upo" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 6upo" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Fumarase\|Fumarase]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: Fumarate hydratase]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Leishmania major ~~mhom/il/81/friedlin~~]]	+	[[Category: Leishmania major strain Friedlin]]
-	[[Category: Drennan~~, C L~~]]	+	[[Category: Drennan CL]]
-	[[Category: Feliciano~~, P R]]~~	+	[[Category: Feliciano PR]]
-	~~[[Category: Fumarase]]~~	+
-	~~[[Category: Leishmania major]]~~	+
-	~~[[Category: Lyase]]~~	+
-	~~[[Category: S-malate]]~~	+
-	~~[[Category: Substrate]]~~	+
-	~~[[Category: Variant h334a~~]]	+

OCA at 13:25, 18 December 2019

2019-12-18T13:25:26Z

←Older revision		Revision as of 13:25, 18 December 2019
Line 3:		Line 3:
	<StructureSection load='6upo' size='340' side='right'caption='[[6upo]], [[Resolution\|resolution]] 3.11Å' scene=''>		<StructureSection load='6upo' size='340' side='right'caption='[[6upo]], [[Resolution\|resolution]] 3.11Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6upo]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6UPO OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6UPO FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6upo]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Leishmania_major_mhom/il/81/friedlin Leishmania major mhom/il/81/friedlin]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6UPO OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6UPO FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=LMR:(2S)-2-HYDROXYBUTANEDIOIC+ACID'>LMR</scene>, <scene name='pdbligand=SF4:IRON/SULFUR+CLUSTER'>SF4</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=LMR:(2S)-2-HYDROXYBUTANEDIOIC+ACID'>LMR</scene>, <scene name='pdbligand=SF4:IRON/SULFUR+CLUSTER'>SF4</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[6unz\|6unz]], [[6uo0\|6uo0]], [[6uoi\|6uoi]], [[6uoj\|6uoj]], [[6up9\|6up9]], [[6upm\|6upm]], [[6uq8\|6uq8]], [[6uq9\|6uq9]], [[6uqb\|6uqb]], [[6uql\|6uql]], [[6uqm\|6uqm]], [[6uqn\|6uqn]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[6unz\|6unz]], [[6uo0\|6uo0]], [[6uoi\|6uoi]], [[6uoj\|6uoj]], [[6up9\|6up9]], [[6upm\|6upm]], [[6uq8\|6uq8]], [[6uq9\|6uq9]], [[6uqb\|6uqb]], [[6uql\|6uql]], [[6uqm\|6uqm]], [[6uqn\|6uqn]]</td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">FH2, LMJF_29_1960 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=347515 Leishmania major MHOM/IL/81/Friedlin])</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Fumarate_hydratase Fumarate hydratase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.2.1.2 4.2.1.2] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Fumarate_hydratase Fumarate hydratase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.2.1.2 4.2.1.2] </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=6upo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6upo OCA], [http://pdbe.org/6upo PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6upo RCSB], [http://www.ebi.ac.uk/pdbsum/6upo PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6upo 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=6upo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6upo OCA], [http://pdbe.org/6upo PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6upo RCSB], [http://www.ebi.ac.uk/pdbsum/6upo PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6upo ProSAT]</span></td></tr>
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	[[Category: Fumarate hydratase]]		[[Category: Fumarate hydratase]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
		+	[[Category: Leishmania major mhom/il/81/friedlin]]
	[[Category: Drennan, C L]]		[[Category: Drennan, C L]]
	[[Category: Feliciano, P R]]		[[Category: Feliciano, P R]]

OCA at 08:26, 4 December 2019

2019-12-04T08:26:37Z

←Older revision		Revision as of 08:26, 4 December 2019
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 6upo is ~~ON HOLD until Paper~~ Publication	+	==Crystal structure of H334A variant of cytosolic fumarate hydratase from Leishmania major in a complex with S-malate==
		+	<StructureSection load='6upo' size='340' side='right'caption='[[6upo]], [[Resolution\|resolution]] 3.11Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[6upo]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6UPO OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6UPO FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=LMR:(2S)-2-HYDROXYBUTANEDIOIC+ACID'>LMR</scene>, <scene name='pdbligand=SF4:IRON/SULFUR+CLUSTER'>SF4</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[6unz\|6unz]], [[6uo0\|6uo0]], [[6uoi\|6uoi]], [[6uoj\|6uoj]], [[6up9\|6up9]], [[6upm\|6upm]], [[6uq8\|6uq8]], [[6uq9\|6uq9]], [[6uqb\|6uqb]], [[6uql\|6uql]], [[6uqm\|6uqm]], [[6uqn\|6uqn]]</td></tr>
		+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Fumarate_hydratase Fumarate hydratase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.2.1.2 4.2.1.2] </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=6upo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6upo OCA], [http://pdbe.org/6upo PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6upo RCSB], [http://www.ebi.ac.uk/pdbsum/6upo PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6upo ProSAT]</span></td></tr>
		+	</table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Class I fumarate hydratases (FHs) are central metabolic enzymes that use a [4Fe-4S] cluster to catalyze the reversible conversion of fumarate to S-malate. The parasite Leishmania major, which is responsible for leishmaniasis, expresses two class I FH isoforms: mitochondrial LmFH-1 and cytosolic LmFH-2. In this study, we present kinetic characterizations of both LmFH isoforms, present 13 crystal structures of LmFH-2 variants, and employ site-directed mutagenesis to investigate the enzyme's mechanism. Our kinetic data confirm that both LmFH-1 and LmFH-2 are susceptible to oxygen-dependent inhibition, with data from crystallography and electron paramagnetic resonance spectroscopy showing that oxygen exposure converts an active [4Fe-4S] cluster to an inactive [3Fe-4S] cluster. Our anaerobically conducted kinetic studies reveal a preference for fumarate over S-malate. Our data further reveal that single alanine substitutions of T467, R421, R471, D135, and H334 decrease kcat values 9-16000-fold without substantially affecting Km values, suggesting that these residues function in catalytic roles. Crystal structures of LmFH-2 variants are consistent with this idea, showing similar bidentate binding to the unique iron of the [4Fe-4S] cluster for substrate S-malate as observed in wild type FH. We further present LmFH-2 structures with substrate fumarate and weak inhibitors succinate and malonate bound in the active site and the first structure of an LmFH that is substrate-free and inhibitor-free, the latter showing increased mobility in the C-terminal domain. Collectively, these data provide insight into the molecular basis for the reaction catalyzed by LmFHs, enzymes that are potential drug targets against leishmaniasis.

-	~~Authors~~:	+	Structural and Biochemical Investigations of the [4Fe-4S] Cluster-Containing Fumarate Hydratase from Leishmania major.,Feliciano PR, Drennan CL Biochemistry. 2019 Nov 27. doi: 10.1021/acs.biochem.9b00923. PMID:31743022<ref>PMID:31743022</ref>

-	~~Description~~:	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased~~ Structures]]	+	</div>
		+	<div class="pdbe-citations 6upo" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Fumarate hydratase]]
		+	[[Category: Large Structures]]
		+	[[Category: Drennan, C L]]
		+	[[Category: Feliciano, P R]]
		+	[[Category: Fumarase]]
		+	[[Category: Leishmania major]]
		+	[[Category: Lyase]]
		+	[[Category: S-malate]]
		+	[[Category: Substrate]]
		+	[[Category: Variant h334a]]

OCA at 07:38, 30 October 2019

2019-10-30T07:38:25Z

←Older revision		Revision as of 07:38, 30 October 2019
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 6upo is ON HOLD	+	The entry 6upo is ON HOLD until Paper Publication

	Authors:		Authors:

OCA: Protected "6upo" [edit=sysop:move=sysop]

2019-10-23T05:20:24Z

Protected "6upo" [edit=sysop:move=sysop]

←Older revision

Revision as of 05:20, 23 October 2019

OCA: New page: '''Unreleased structure''' The entry 6upo is ON HOLD Authors: Description: Category: Unreleased Structures

2019-10-23T05:20:22Z

New page: '''Unreleased structure''' The entry 6upo is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 6upo is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]