5x6f - Revision history

OCA at 10:17, 27 March 2024

OCA — Wed, 27 Mar 2024 10:17:24 GMT

←Older revision		Revision as of 10:17, 27 March 2024
Line 1:		Line 1:

	==Crystal structure of Phosphopantetheine adenylyltransferase from Pseudomonas aeruginosa==		==Crystal structure of Phosphopantetheine adenylyltransferase from Pseudomonas aeruginosa==
-	<StructureSection load='5x6f' size='340' side='right' caption='[[5x6f]], [[Resolution\|resolution]] 2.59Å' scene=''>	+	<StructureSection load='5x6f' size='340' side='right'caption='[[5x6f]], [[Resolution\|resolution]] 2.59Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5x6f]] is a 6 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~Pseae Pseae~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5X6F OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5X6F FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5x6f]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Pseudomonas_aeruginosa_PAO1 Pseudomonas aeruginosa PAO1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5X6F OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5X6F FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat"~~><scene name~~=~~'pdbligand=GOL:GLYCEROL'>GOL</scene~~>, ~~<scene name='pdbligand=IPA:ISOPROPYL+ALCOHOL'>IPA</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]] 2.593Å</td></tr>
-	<tr id='~~gene~~'><td class="sblockLbl"><b>[[~~Gene~~\|~~Gene~~:]]</b></td><td class="sblockDat"~~>coaD, PA0363 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&~~id=~~208964 PSEAE])</td~~><~~/tr>~~	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=IPA:ISOPROPYL+ALCOHOL'>IPA</scene></td></tr>
-	~~<tr id~~='~~activity'><td class~~=~~"sblockLbl"><b>Activity~~:~~</b~~></td><~~td class~~=~~"sblockDat"><span class~~=~~'plainlinks~~'>[http://en.wikipedia.org/wiki/Pantetheine-phosphate_adenylyltransferase Pantetheine-phosphate adenylyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.3 2.7.7.3] </~~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=5x6f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5x6f OCA], [https://pdbe.org/5x6f PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5x6f RCSB], [https://www.ebi.ac.uk/pdbsum/5x6f PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5x6f 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=5x6f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5x6f OCA], [~~http~~://pdbe.org/5x6f PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5x6f RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5x6f PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5x6f ProSAT]</span></td></tr>	+
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/COAD_PSEAE COAD_PSEAE]] Reversibly transfers an adenylyl group from ATP to 4'-phosphopantetheine, yielding dephospho-CoA (dPCoA) and pyrophosphate.	+	[https://www.uniprot.org/uniprot/COAD_PSEAE COAD_PSEAE] Reversibly transfers an adenylyl group from ATP to 4'-phosphopantetheine, yielding dephospho-CoA (dPCoA) and pyrophosphate.
-	~~<div style="background-color:#fffaf0;">~~	+
-	~~== Publication Abstract from PubMed ==~~	+
-	Phosphopantetheine adenylyltransferase (PPAT) is a rate-limiting enzyme essential for biosynthesis of coenzyme A (CoA), which in turn is responsible to regulate the secretion of exotoxins via type III secretion system in Pseudomonas aeruginosa, causing severe health concerns ranging from nosocomial infections to respiratory failure. Acetyl coenzyme A (AcCoA) is a newly reported inhibitor of PPAT, believed to regulate the cellular levels of CoA and thereby the pathogenesis. Very little is known so far regarding the mechanistic details of AcCoA binding inside PPAT-binding cleft. Herein, we have used extensive umbrella sampling simulations to decipher mechanistic insight into the inhibitor accommodation inside the binding cavity. We found that R90 and D94 residues act like a gate near the binding cavity to accommodate and stabilize the incoming ligand. Mutational models concerning these residues also show considerable difference in AcCoA-binding thermodynamics. To substantiate our findings, we have solved the first crystal structure of apo-PPAT from P. aeruginosa, which also found to agree with the simulation results. Collectively, these results describe the mechanistic details of accommodation of inhibitor molecule inside PPAT-binding cavity and also offer valuable insight into regulating cellular levels of CoA/AcCoA and thus controlling the pathogenicity.	+
-		+
-	Umbrella Sampling and X-ray Crystallographic Analysis Unveil an Arg-Asp Gate Facilitating Inhibitor Binding Inside Phosphopantetheine Adenylyltransferase Allosteric Cleft.,Mondal A, Chatterjee R, Datta S J Phys Chem B. 2018 Feb 8;122(5):1551-1559. doi: 10.1021/acs.jpcb.7b09543. Epub, 2018 Jan 30. PMID:29345931<ref>PMID:29345931</ref>	+
-		+
-	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~	+
-	~~</div>~~	+
-	~~<div class="pdbe-citations 5x6f" style="background-color:#fffaf0;"></div>~~	+
-	~~== References ==~~	+
-	~~<references/>~~	+
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Pantetheine-phosphate adenylyltransferase~~]]	+	[[Category: Large Structures]]
-	[[Category: ~~Pseae~~]]	+	[[Category: Pseudomonas aeruginosa PAO1]]
-	[[Category: Chatterjee, R]]	+	[[Category: Chatterjee R]]
-	[[Category: Datta, S]]	+	[[Category: Datta S]]
-	[[Category: Mondal, A]]	+	[[Category: Mondal A]]
-	~~[[Category: Phosphopantetheine adenylyltransferase]]~~	+
-	~~[[Category: Pseudomonas aeruginosa]]~~	+
-	~~[[Category: Transferase~~]]	+

OCA at 08:23, 22 February 2018

OCA — Thu, 22 Feb 2018 08:23:29 GMT

←Older revision		Revision as of 08:23, 22 February 2018
Line 3:		Line 3:
	<StructureSection load='5x6f' size='340' side='right' caption='[[5x6f]], [[Resolution\|resolution]] 2.59Å' scene=''>		<StructureSection load='5x6f' size='340' side='right' caption='[[5x6f]], [[Resolution\|resolution]] 2.59Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5x6f]] is a 6 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5X6F OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5X6F FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5x6f]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Pseae Pseae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5X6F OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5X6F FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=IPA:ISOPROPYL+ALCOHOL'>IPA</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=IPA:ISOPROPYL+ALCOHOL'>IPA</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">coaD, PA0363 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=208964 PSEAE])</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Pantetheine-phosphate_adenylyltransferase Pantetheine-phosphate adenylyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.3 2.7.7.3] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Pantetheine-phosphate_adenylyltransferase Pantetheine-phosphate adenylyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.3 2.7.7.3] </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=5x6f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5x6f OCA], [http://pdbe.org/5x6f PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5x6f RCSB], [http://www.ebi.ac.uk/pdbsum/5x6f PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5x6f 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=5x6f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5x6f OCA], [http://pdbe.org/5x6f PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5x6f RCSB], [http://www.ebi.ac.uk/pdbsum/5x6f PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5x6f ProSAT]</span></td></tr>
Line 24:		Line 25:
	</StructureSection>		</StructureSection>
	[[Category: Pantetheine-phosphate adenylyltransferase]]		[[Category: Pantetheine-phosphate adenylyltransferase]]
		+	[[Category: Pseae]]
	[[Category: Chatterjee, R]]		[[Category: Chatterjee, R]]
	[[Category: Datta, S]]		[[Category: Datta, S]]

OCA at 06:29, 15 February 2018

OCA — Thu, 15 Feb 2018 06:29:56 GMT

←Older revision		Revision as of 06:29, 15 February 2018
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 5x6f is ~~ON HOLD until Paper~~ Publication	+	==Crystal structure of Phosphopantetheine adenylyltransferase from Pseudomonas aeruginosa==
		+	<StructureSection load='5x6f' size='340' side='right' caption='[[5x6f]], [[Resolution\|resolution]] 2.59Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[5x6f]] is a 6 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5X6F OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5X6F FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=IPA:ISOPROPYL+ALCOHOL'>IPA</scene></td></tr>
		+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Pantetheine-phosphate_adenylyltransferase Pantetheine-phosphate adenylyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.3 2.7.7.3] </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=5x6f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5x6f OCA], [http://pdbe.org/5x6f PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5x6f RCSB], [http://www.ebi.ac.uk/pdbsum/5x6f PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5x6f ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/COAD_PSEAE COAD_PSEAE]] Reversibly transfers an adenylyl group from ATP to 4'-phosphopantetheine, yielding dephospho-CoA (dPCoA) and pyrophosphate.
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Phosphopantetheine adenylyltransferase (PPAT) is a rate-limiting enzyme essential for biosynthesis of coenzyme A (CoA), which in turn is responsible to regulate the secretion of exotoxins via type III secretion system in Pseudomonas aeruginosa, causing severe health concerns ranging from nosocomial infections to respiratory failure. Acetyl coenzyme A (AcCoA) is a newly reported inhibitor of PPAT, believed to regulate the cellular levels of CoA and thereby the pathogenesis. Very little is known so far regarding the mechanistic details of AcCoA binding inside PPAT-binding cleft. Herein, we have used extensive umbrella sampling simulations to decipher mechanistic insight into the inhibitor accommodation inside the binding cavity. We found that R90 and D94 residues act like a gate near the binding cavity to accommodate and stabilize the incoming ligand. Mutational models concerning these residues also show considerable difference in AcCoA-binding thermodynamics. To substantiate our findings, we have solved the first crystal structure of apo-PPAT from P. aeruginosa, which also found to agree with the simulation results. Collectively, these results describe the mechanistic details of accommodation of inhibitor molecule inside PPAT-binding cavity and also offer valuable insight into regulating cellular levels of CoA/AcCoA and thus controlling the pathogenicity.

-	~~Authors~~:	+	Umbrella Sampling and X-ray Crystallographic Analysis Unveil an Arg-Asp Gate Facilitating Inhibitor Binding Inside Phosphopantetheine Adenylyltransferase Allosteric Cleft.,Mondal A, Chatterjee R, Datta S J Phys Chem B. 2018 Feb 8;122(5):1551-1559. doi: 10.1021/acs.jpcb.7b09543. Epub, 2018 Jan 30. PMID:29345931<ref>PMID:29345931</ref>

-	~~Description~~:	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased Structures~~]]	+	</div>
		+	<div class="pdbe-citations 5x6f" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Pantetheine-phosphate adenylyltransferase]]
		+	[[Category: Chatterjee, R]]
		+	[[Category: Datta, S]]
		+	[[Category: Mondal, A]]
		+	[[Category: Phosphopantetheine adenylyltransferase]]
		+	[[Category: Pseudomonas aeruginosa]]
		+	[[Category: Transferase]]

OCA at 20:13, 15 March 2017

OCA — Wed, 15 Mar 2017 20:13:56 GMT

←Older revision		Revision as of 20:13, 15 March 2017
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 5x6f is ON HOLD	+	The entry 5x6f is ON HOLD until Paper Publication

	Authors:		Authors:

OCA: Protected "5x6f" [edit=sysop:move=sysop]

OCA — Thu, 09 Mar 2017 15:48:54 GMT

Protected "5x6f" [edit=sysop:move=sysop]

←Older revision

Revision as of 15:48, 9 March 2017

OCA: New page: '''Unreleased structure''' The entry 5x6f is ON HOLD Authors: Description: Category: Unreleased Structures

OCA — Thu, 09 Mar 2017 15:48:53 GMT

New page: '''Unreleased structure''' The entry 5x6f is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 5x6f is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]