6qu4 - Revision history

OCA at 12:08, 24 January 2024

OCA — Wed, 24 Jan 2024 12:08:48 GMT

←Older revision		Revision as of 12:08, 24 January 2024
Line 3:		Line 3:
	<StructureSection load='6qu4' size='340' side='right'caption='[[6qu4]], [[Resolution\|resolution]] 2.75Å' scene=''>		<StructureSection load='6qu4' size='340' side='right'caption='[[6qu4]], [[Resolution\|resolution]] 2.75Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6qu4]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/~~Trybb Trybb~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6QU4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6QU4 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6qu4]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Trypanosoma_brucei_brucei Trypanosoma brucei brucei]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6QU4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6QU4 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CIT:CITRIC+ACID'>CIT</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=JJ2:1-[(3,4-dichlorophenyl)methyl]-5-[2-(dimethylamino)ethyl]pyrrolo[3,2-c]pyridin-4-one'>JJ2</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]] 2.75Å</td></tr>
-	~~<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">pfk ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=5702 TRYBB])</td></tr>~~	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CIT:CITRIC+ACID'>CIT</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=JJ2:1-[(3,4-dichlorophenyl)methyl]-5-[2-(dimethylamino)ethyl]pyrrolo[3,2-c]pyridin-4-one'>JJ2</scene></td></tr>
-	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/6-phosphofructokinase 6-phosphofructokinase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.11 2.7.1.11] </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=6qu4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6qu4 OCA], [https://pdbe.org/6qu4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6qu4 RCSB], [https://www.ebi.ac.uk/pdbsum/6qu4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6qu4 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=6qu4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6qu4 OCA], [https://pdbe.org/6qu4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6qu4 RCSB], [https://www.ebi.ac.uk/pdbsum/6qu4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6qu4 ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[https://www.uniprot.org/uniprot/PFKA_TRYBB PFKA_TRYBB]] Catalyzes the phosphorylation of D-fructose 6-phosphate to fructose 1,6-bisphosphate by ATP, the first committing step of glycolysis.[HAMAP-Rule:MF_03186]	+	[https://www.uniprot.org/uniprot/PFKA_TRYBB PFKA_TRYBB] Catalyzes the phosphorylation of D-fructose 6-phosphate to fructose 1,6-bisphosphate by ATP, the first committing step of glycolysis.[HAMAP-Rule:MF_03186]
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 27:		Line 26:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: 6-phosphofructokinase]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: ~~Trybb~~]]	+	[[Category: Trypanosoma brucei brucei]]
-	[[Category: Dornan, J]]	+	[[Category: Dornan J]]
-	[[Category: McNae~~, I W~~]]	+	[[Category: McNae IW]]
-	[[Category: Walkinshaw~~, M D]]~~	+	[[Category: Walkinshaw MD]]
-	~~[[Category: Allostery]]~~	+
-	~~[[Category: Glycolysis]]~~	+
-	~~[[Category: Inhibitor]]~~	+
-	~~[[Category: Transferase~~]]	+

OCA at 14:54, 3 March 2021

OCA — Wed, 03 Mar 2021 14:54:54 GMT

←Older revision		Revision as of 14:54, 3 March 2021
Line 3:		Line 3:
	<StructureSection load='6qu4' size='340' side='right'caption='[[6qu4]], [[Resolution\|resolution]] 2.75Å' scene=''>		<StructureSection load='6qu4' size='340' side='right'caption='[[6qu4]], [[Resolution\|resolution]] 2.75Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6qu4]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6QU4 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6QU4 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6qu4]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Trybb Trybb]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6QU4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6QU4 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CIT:CITRIC+ACID'>CIT</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=JJ2:1-[(3,4-dichlorophenyl)methyl]-5-[2-(dimethylamino)ethyl]pyrrolo[3,2-c]pyridin-4-one'>JJ2</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CIT:CITRIC+ACID'>CIT</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=JJ2:1-[(3,4-dichlorophenyl)methyl]-5-[2-(dimethylamino)ethyl]pyrrolo[3,2-c]pyridin-4-one'>JJ2</scene></td></tr>
-	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://en.wikipedia.org/wiki/6-phosphofructokinase 6-phosphofructokinase], with EC number [~~http~~://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.11 2.7.1.11] </span></td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">pfk ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=5702 TRYBB])</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=6qu4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6qu4 OCA], [~~http~~://pdbe.org/6qu4 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6qu4 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6qu4 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6qu4 ProSAT]</span></td></tr>	+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/6-phosphofructokinase 6-phosphofructokinase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.11 2.7.1.11] </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=6qu4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6qu4 OCA], [https://pdbe.org/6qu4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6qu4 RCSB], [https://www.ebi.ac.uk/pdbsum/6qu4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6qu4 ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[~~http~~://www.uniprot.org/uniprot/PFKA_TRYBB PFKA_TRYBB]] Catalyzes the phosphorylation of D-fructose 6-phosphate to fructose 1,6-bisphosphate by ATP, the first committing step of glycolysis.[HAMAP-Rule:MF_03186]	+	[[https://www.uniprot.org/uniprot/PFKA_TRYBB PFKA_TRYBB]] Catalyzes the phosphorylation of D-fructose 6-phosphate to fructose 1,6-bisphosphate by ATP, the first committing step of glycolysis.[HAMAP-Rule:MF_03186]
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The parasitic protist Trypanosoma brucei is the causative agent of Human African Trypanosomiasis, also known as sleeping sickness. The parasite enters the blood via the bite of the tsetse fly where it is wholly reliant on glycolysis for the production of ATP. Glycolytic enzymes have been regarded as challenging drug targets because of their highly conserved active sites and phosphorylated substrates. We describe the development of novel small molecule allosteric inhibitors of trypanosome phosphofructokinase (PFK) that block the glycolytic pathway resulting in very fast parasite kill times with no inhibition of human PFKs. The compounds cross the blood brain barrier and single day oral dosing cures parasitaemia in a stage 1 animal model of human African trypanosomiasis. This study demonstrates that it is possible to target glycolysis and additionally shows how differences in allosteric mechanisms may allow the development of species-specific inhibitors to tackle a range of proliferative or infectious diseases.
		+
		+	Fast acting allosteric phosphofructokinase inhibitors block trypanosome glycolysis and cure acute African trypanosomiasis in mice.,McNae IW, Kinkead J, Malik D, Yen LH, Walker MK, Swain C, Webster SP, Gray N, Fernandes PM, Myburgh E, Blackburn EA, Ritchie R, Austin C, Wear MA, Highton AJ, Keats AJ, Vong A, Dornan J, Mottram JC, Michels PAM, Pettit S, Walkinshaw MD Nat Commun. 2021 Feb 16;12(1):1052. doi: 10.1038/s41467-021-21273-6. PMID:33594070<ref>PMID:33594070</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 6qu4" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Phosphofructokinase 3D structures\|Phosphofructokinase 3D structures]]
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: 6-phosphofructokinase]]		[[Category: 6-phosphofructokinase]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
		+	[[Category: Trybb]]
	[[Category: Dornan, J]]		[[Category: Dornan, J]]
	[[Category: McNae, I W]]		[[Category: McNae, I W]]

OCA at 09:48, 18 March 2020

OCA — Wed, 18 Mar 2020 09:48:19 GMT

←Older revision		Revision as of 09:48, 18 March 2020
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 6qu4 is ~~ON HOLD~~	+	==Crystal Structure of Phosphofructokinase from Trypanosoma brucei in complex with an allosteric inhibitor ctcb405==
-		+	<StructureSection load='6qu4' size='340' side='right'caption='[[6qu4]], [[Resolution\|resolution]] 2.75Å' scene=''>
-	~~Authors~~: ~~McNae~~, I.W., ~~Dornan~~, J., ~~Walkinshaw~~, M.D.	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[6qu4]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6QU4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6QU4 FirstGlance]. <br>
-	~~Description~~: ~~Crystal Structure~~ of ~~Phosphofructokinase from Trypanosoma brucei in complex with an allosteric inhibitor ctcb405~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CIT:CITRIC+ACID'>CIT</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=JJ2:1-[(3,4-dichlorophenyl)methyl]-5-[2-(dimethylamino)ethyl]pyrrolo[3,2-c]pyridin-4-one'>JJ2</scene></td></tr>
-	[[Category: ~~Unreleased Structures~~]]	+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/6-phosphofructokinase 6-phosphofructokinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.11 2.7.1.11] </span></td></tr>
-	[[Category: ~~Mcnae, I.W~~]]	+	<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=6qu4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6qu4 OCA], [http://pdbe.org/6qu4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6qu4 RCSB], [http://www.ebi.ac.uk/pdbsum/6qu4 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6qu4 ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/PFKA_TRYBB PFKA_TRYBB]] Catalyzes the phosphorylation of D-fructose 6-phosphate to fructose 1,6-bisphosphate by ATP, the first committing step of glycolysis.[HAMAP-Rule:MF_03186]
		+	__TOC__
		+	</StructureSection>
		+	[[Category: 6-phosphofructokinase]]
		+	[[Category: Large Structures]]
	[[Category: Dornan, J]]		[[Category: Dornan, J]]
-	[[Category: Walkinshaw, M.D]]	+	[[Category: McNae, I W]]
		+	[[Category: Walkinshaw, M D]]
		+	[[Category: Allostery]]
		+	[[Category: Glycolysis]]
		+	[[Category: Inhibitor]]
		+	[[Category: Transferase]]

OCA: Protected "6qu4" [edit=sysop:move=sysop]

OCA — Wed, 06 Mar 2019 05:55:29 GMT

Protected "6qu4" [edit=sysop:move=sysop]

←Older revision

Revision as of 05:55, 6 March 2019

OCA: New page: '''Unreleased structure''' The entry 6qu4 is ON HOLD Authors: McNae, I.W., Dornan, J., Walkinshaw, M.D. Description: Crystal Structure of Phosphofructokinase from Trypanosoma brucei in...

OCA — Wed, 06 Mar 2019 05:55:27 GMT

New page: '''Unreleased structure''' The entry 6qu4 is ON HOLD Authors: McNae, I.W., Dornan, J., Walkinshaw, M.D. Description: Crystal Structure of Phosphofructokinase from Trypanosoma brucei in...

New page

'''Unreleased structure'''

The entry 6qu4 is ON HOLD

Authors: McNae, I.W., Dornan, J., Walkinshaw, M.D.

Description: Crystal Structure of Phosphofructokinase from Trypanosoma brucei in complex with an allosteric inhibitor ctcb405
[[Category: Unreleased Structures]]
[[Category: Mcnae, I.W]]
[[Category: Dornan, J]]
[[Category: Walkinshaw, M.D]]