7bes - Revision history

OCA at 11:01, 31 August 2022

OCA — Wed, 31 Aug 2022 11:01:21 GMT

←Older revision		Revision as of 11:01, 31 August 2022
Line 1:		Line 1:

	==CryoEM structure of Mycobacterium tuberculosis UMP Kinase (UMPK) in complex with UDP and UTP==		==CryoEM structure of Mycobacterium tuberculosis UMP Kinase (UMPK) in complex with UDP and UTP==
-	<StructureSection load='7bes' size='340' side='right'caption='[[7bes]]~~, [[Resolution\|resolution]] 2.85Å~~' scene=''>	+	<StructureSection load='7bes' size='340' side='right'caption='[[7bes]]' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>~~[[7bes]] is a 3 chain structure.~~ Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7BES OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7BES FirstGlance]. <br>	+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7BES OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7BES FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=UDP:URIDINE-5-DIPHOSPHATE'>UDP</scene>, <scene name='pdbligand=UTP:URIDINE+5-TRIPHOSPHATE'>UTP</scene></td></tr>	+	</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=7bes FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7bes OCA], [https://pdbe.org/7bes PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7bes RCSB], [https://www.ebi.ac.uk/pdbsum/7bes PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7bes 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/UMP_kinase UMP kinase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.4.22 2.7.4.22] </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=7bes FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7bes OCA], [https://pdbe.org/7bes PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7bes RCSB], [https://www.ebi.ac.uk/pdbsum/7bes PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7bes ProSAT]</span></td></tr>	+
	</table>		</table>
-	== Function ==
-	[[https://www.uniprot.org/uniprot/A0A045IH65_MYCTX A0A045IH65_MYCTX]] Catalyzes the reversible phosphorylation of UMP to UDP.[HAMAP-Rule:MF_01220]
-	<div style="background-color:#fffaf0;">
-	== Publication Abstract from PubMed ==
-	Tuberculosis claims significantly more than one million lives each year. A feasible way to face the issue of drug resistance is the development of new antibiotics. Bacterial uridine 5'-monophosphate (UMP) kinase is a promising target for novel antibiotic discovery as it is essential for bacterial survival and has no counterpart in human cells. The UMP kinase from M. tuberculosis is also a model of particular interest for allosteric regulation with two effectors, GTP (positive) and UTP (negative). In this study, using X-ray crystallography and cryo-electron microscopy, we report for the first time a detailed description of the negative effector UTP-binding site of a typical Gram-positive behaving UMP kinase. Comparison between this snapshot of low affinity for Mg-ATP with our previous 3D-structure of the GTP-bound complex of high affinity for Mg-ATP led to a better understanding of the cooperative mechanism and the allosteric regulation of UMP kinase. Thermal shift assay and circular dichroism experiments corroborate our model of an inhibition by UTP linked to higher flexibility of the Mg-ATP-binding domain. These new structural insights provide valuable knowledge for future drug discovery strategies targeting bacterial UMP kinases.
-
-	Structural basis for the allosteric inhibition of UMP kinase from Gram-positive bacteria, a promising antibacterial target.,Walter P, Mechaly A, Bous J, Haouz A, England P, Lai-Kee-Him J, Ancelin A, Hoos S, Baron B, Trapani S, Bron P, Labesse G, Munier-Lehmann H FEBS J. 2022 Feb 12. doi: 10.1111/febs.16393. PMID:35152545<ref>PMID:35152545</ref>
-
-	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	</div>
-	<div class="pdbe-citations 7bes" style="background-color:#fffaf0;"></div>
-	== References ==
-	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	~~[[Category: UMP kinase]]~~	+	[[Category: Bous J]]
-	[[Category: Bous, J]]	+	[[Category: Bron P]]
-	[[Category: Bron, P]]	+	[[Category: Munier-Lehmann H]]
-	[[Category: Munier-Lehmann, H]]	+	[[Category: Trapani S]]
-	[[Category: Trapani, S]]	+	[[Category: Walter P]]
-	[[Category: Walter, P]]	+
-	~~[[Category: Allosteric regulation]]~~	+
-	~~[[Category: Antibacterial target]]~~	+
-	~~[[Category: Nucleotide metabolism]]~~	+
-	~~[[Category: Transferase]]~~	+
-	~~[[Category: Ump kinase~~]]	+

OCA at 07:13, 16 March 2022

OCA — Wed, 16 Mar 2022 07:13:18 GMT

←Older revision		Revision as of 07:13, 16 March 2022
Line 1:		Line 1:

	==CryoEM structure of Mycobacterium tuberculosis UMP Kinase (UMPK) in complex with UDP and UTP==		==CryoEM structure of Mycobacterium tuberculosis UMP Kinase (UMPK) in complex with UDP and UTP==
-	<StructureSection load='7bes' size='340' side='right'caption='[[7bes]]' scene=''>	+	<StructureSection load='7bes' size='340' side='right'caption='[[7bes]], [[Resolution\|resolution]] 2.85Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7BES OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7BES FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7bes]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7BES OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7BES FirstGlance]. <br>
-	</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=7bes FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7bes OCA], [https://pdbe.org/7bes PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7bes RCSB], [https://www.ebi.ac.uk/pdbsum/7bes PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7bes ProSAT]</span></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=UDP:URIDINE-5-DIPHOSPHATE'>UDP</scene>, <scene name='pdbligand=UTP:URIDINE+5-TRIPHOSPHATE'>UTP</scene></td></tr>
		+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/UMP_kinase UMP kinase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.4.22 2.7.4.22] </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=7bes FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7bes OCA], [https://pdbe.org/7bes PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7bes RCSB], [https://www.ebi.ac.uk/pdbsum/7bes PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7bes ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[[https://www.uniprot.org/uniprot/A0A045IH65_MYCTX A0A045IH65_MYCTX]] Catalyzes the reversible phosphorylation of UMP to UDP.[HAMAP-Rule:MF_01220]
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Tuberculosis claims significantly more than one million lives each year. A feasible way to face the issue of drug resistance is the development of new antibiotics. Bacterial uridine 5'-monophosphate (UMP) kinase is a promising target for novel antibiotic discovery as it is essential for bacterial survival and has no counterpart in human cells. The UMP kinase from M. tuberculosis is also a model of particular interest for allosteric regulation with two effectors, GTP (positive) and UTP (negative). In this study, using X-ray crystallography and cryo-electron microscopy, we report for the first time a detailed description of the negative effector UTP-binding site of a typical Gram-positive behaving UMP kinase. Comparison between this snapshot of low affinity for Mg-ATP with our previous 3D-structure of the GTP-bound complex of high affinity for Mg-ATP led to a better understanding of the cooperative mechanism and the allosteric regulation of UMP kinase. Thermal shift assay and circular dichroism experiments corroborate our model of an inhibition by UTP linked to higher flexibility of the Mg-ATP-binding domain. These new structural insights provide valuable knowledge for future drug discovery strategies targeting bacterial UMP kinases.
		+
		+	Structural basis for the allosteric inhibition of UMP kinase from Gram-positive bacteria, a promising antibacterial target.,Walter P, Mechaly A, Bous J, Haouz A, England P, Lai-Kee-Him J, Ancelin A, Hoos S, Baron B, Trapani S, Bron P, Labesse G, Munier-Lehmann H FEBS J. 2022 Feb 12. doi: 10.1111/febs.16393. PMID:35152545<ref>PMID:35152545</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7bes" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Bous J]]	+	[[Category: UMP kinase]]
-	[[Category: Bron P]]	+	[[Category: Bous, J]]
-	[[Category: Munier-Lehmann H]]	+	[[Category: Bron, P]]
-	[[Category: Trapani S]]	+	[[Category: Munier-Lehmann, H]]
-	[[Category: Walter P]]	+	[[Category: Trapani, S]]
		+	[[Category: Walter, P]]
		+	[[Category: Allosteric regulation]]
		+	[[Category: Antibacterial target]]
		+	[[Category: Nucleotide metabolism]]
		+	[[Category: Transferase]]
		+	[[Category: Ump kinase]]

OCA at 09:55, 12 January 2022

OCA — Wed, 12 Jan 2022 09:55:28 GMT

←Older revision		Revision as of 09:55, 12 January 2022
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 7bes ~~is ON HOLD until Paper Publication~~	+	==CryoEM structure of Mycobacterium tuberculosis UMP Kinase (UMPK) in complex with UDP and UTP==
-		+	<StructureSection load='7bes' size='340' side='right'caption='[[7bes]]' scene=''>
-	~~Authors~~: ~~Bous~~, J., ~~Trapani, S~~., ~~Walter, P~~., ~~Bron, P~~., ~~Munier~~-~~Lehmann, H~~.	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7BES OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7BES FirstGlance]. <br>
-	~~Description: CryoEM structure of Mycobacterium tuberculosis UMP Kinase (UMPK) in complex with UDP and UTP~~	+	</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=7bes FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7bes OCA], [https://pdbe.org/7bes PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7bes RCSB], [https://www.ebi.ac.uk/pdbsum/7bes PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7bes ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	</table>
-	[[Category: Bous, J]]	+	__TOC__
-	[[Category: ~~Munier-Lehmann, H~~]]	+	</StructureSection>
-	[[Category: ~~Walter, P~~]]	+	[[Category: Large Structures]]
-	[[Category: ~~Bron, P~~]]	+	[[Category: Bous J]]
-	[[Category: ~~Trapani, S~~]]	+	[[Category: Bron P]]
		+	[[Category: Munier-Lehmann H]]
		+	[[Category: Trapani S]]
		+	[[Category: Walter P]]

OCA at 09:04, 10 February 2021

OCA — Wed, 10 Feb 2021 09:04:35 GMT

←Older revision		Revision as of 09:04, 10 February 2021
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 7bes is ON HOLD	+	The entry 7bes is ON HOLD until Paper Publication

	Authors: Bous, J., Trapani, S., Walter, P., Bron, P., Munier-Lehmann, H.		Authors: Bous, J., Trapani, S., Walter, P., Bron, P., Munier-Lehmann, H.

-	Description: CryoEM structure of Mycobacterium tuberculosis ~~UMPK~~ Kinase in complex with UDP and UTP	+	Description: CryoEM structure of Mycobacterium tuberculosis UMP Kinase (UMPK) in complex with UDP and UTP
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
	[[Category: Bous, J]]		[[Category: Bous, J]]

OCA: Protected "7bes" [edit=sysop:move=sysop]

OCA — Wed, 30 Dec 2020 05:20:03 GMT

Protected "7bes" [edit=sysop:move=sysop]

←Older revision

Revision as of 05:20, 30 December 2020

OCA: New page: '''Unreleased structure''' The entry 7bes is ON HOLD Authors: Bous, J., Trapani, S., Walter, P., Bron, P., Munier-Lehmann, H. Description: CryoEM structure of Mycobacterium tuberculosi...

OCA — Wed, 30 Dec 2020 05:20:02 GMT

New page: '''Unreleased structure''' The entry 7bes is ON HOLD Authors: Bous, J., Trapani, S., Walter, P., Bron, P., Munier-Lehmann, H. Description: CryoEM structure of Mycobacterium tuberculosi...

New page

'''Unreleased structure'''

The entry 7bes is ON HOLD

Authors: Bous, J., Trapani, S., Walter, P., Bron, P., Munier-Lehmann, H.

Description: CryoEM structure of Mycobacterium tuberculosis UMPK Kinase in complex with UDP and UTP
[[Category: Unreleased Structures]]
[[Category: Bous, J]]
[[Category: Munier-Lehmann, H]]
[[Category: Walter, P]]
[[Category: Bron, P]]
[[Category: Trapani, S]]