5e0o - Revision history

OCA at 22:08, 28 June 2023

2023-06-28T22:08:49Z

←Older revision		Revision as of 22:08, 28 June 2023
Line 3:		Line 3:
	<StructureSection load='5e0o' size='340' side='right'caption='[[5e0o]], [[Resolution\|resolution]] 3.00Å' scene=''>		<StructureSection load='5e0o' size='340' side='right'caption='[[5e0o]], [[Resolution\|resolution]] 3.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5e0o]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5E0O OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=5E0O FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5e0o]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Brugia_malayi Brugia malayi]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5E0O OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5E0O FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat" id="~~ligandDat~~">~~<scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>~~, ~~<scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 3Å</td></tr>
-	<tr id='~~related~~'><td class="sblockLbl"><b>[[~~Related_structure~~\|~~Related~~:]]</b></td><td class="sblockDat">~~[[4ofz\|4ofz]]~~<~~/td~~></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
-	<~~tr id~~='~~activity'><td class~~=~~"sblockLbl"><b>Activity~~:~~</b~~></td><~~td class~~=~~"sblockDat"><span class~~=~~'plainlinks~~'>~~[http://en.wikipedia.org/wiki/Trehalose-phosphatase Trehalose-phosphatase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.3.12 3.1.3.12]~~ </~~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=5e0o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5e0o OCA], [https://pdbe.org/5e0o PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5e0o RCSB], [https://www.ebi.ac.uk/pdbsum/5e0o PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5e0o ProSAT]</span></td></tr>
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://proteopedia.org/fgij/fg.htm?mol=5e0o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5e0o OCA], [~~http~~://pdbe.org/5e0o PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5e0o RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5e0o PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5e0o ProSAT]</span></td></tr>	+
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/GOB1_BRUMA GOB1_BRUMA]] Catalyzes the hydrolysis of trehalose 6-phosphate to trehalose and phosphate (By similarity).	+	[https://www.uniprot.org/uniprot/GOB1_BRUMA GOB1_BRUMA] Catalyzes the hydrolysis of trehalose 6-phosphate to trehalose and phosphate (By similarity).
-	~~<div style="background-color:#fffaf0;">~~	+
-	~~== Publication Abstract from PubMed ==~~	+
-	Parasitic nematodes are responsible for devastating illnesses that plague many of the world's poorest populations indigenous to the tropical areas of developing nations. Among these diseases is lymphatic filariasis, a major cause of permanent and long-term disability. Proteins essential to nematodes that do not have mammalian counterparts represent targets for therapeutic inhibitor discovery. One promising target is trehalose-6-phosphate phosphatase (T6PP) from Brugia malayi. In the model nematode Caenorhabditis elegans, T6PP is essential for survival due to the toxic effect(s) of the accumulation of trehalose 6-phosphate. T6PP has also been shown to be essential in Mycobacterium tuberculosis. We determined the X-ray crystal structure of T6PP from B. malayi. The protein structure revealed a stabilizing N-terminal MIT-like domain and a catalytic C-terminal C2B-type HAD phosphatase fold. Structure-guided mutagenesis, combined with kinetic analyses using a designed competitive inhibitor, trehalose 6-sulfate, identified five residues important for binding and catalysis. This structure-function analysis along with computational mapping provided the basis for the proposed model of the T6PP-trehalose 6-phosphate complex. The model indicates a substrate-binding mode wherein shape complementarity and van der Waals interactions drive recognition. The mode of binding is in sharp contrast to the homolog sucrose-6-phosphate phosphatase where extensive hydrogen-bond interactions are made to the substrate. Together these results suggest that high-affinity inhibitors will be bi-dentate, taking advantage of substrate-like binding to the phosphoryl-binding pocket while simultaneously utilizing non-native binding to the trehalose pocket. The conservation of the key residues that enforce the shape of the substrate pocket in T6PP enzymes suggest that development of broad-range anthelmintic and antibacterial therapeutics employing this platform may be possible.	+
-		+
-	Structure of the Trehalose-6-phosphate Phosphatase from Brugia malayi Reveals Key Design Principles for Anthelmintic Drugs.,Farelli JD, Galvin BD, Li Z, Liu C, Aono M, Garland M, Hallett OE, Causey TB, Ali-Reynolds A, Saltzberg DJ, Carlow CK, Dunaway-Mariano D, Allen KN PLoS Pathog. 2014 Jul 3;10(7):e1004245. doi: 10.1371/journal.ppat.1004245., eCollection 2014 Jul. PMID:24992307<ref>PMID:24992307</ref>	+
-		+
-	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~	+
-	~~</div>~~	+
-	~~<div class="pdbe-citations 5e0o" style="background-color:#fffaf0;"></div>~~	+
-	~~== References ==~~	+
-	~~<references/>~~	+
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Brugia malayi]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	~~[[Category: Trehalose-phosphatase]]~~	+	[[Category: Agarwal A]]
-	[[Category: Agarwal, A]]	+	[[Category: Misra-Bhattacharya S]]
-	[[Category: Misra-Bhattacharya, S]]	+	[[Category: Ravishankar R]]
-	[[Category: Ravishankar, R]]	+
-	~~[[Category: Complex]]~~	+
-	~~[[Category: Had]]~~	+
-	~~[[Category: Hydrolase]]~~	+
-	~~[[Category: Phosphatase~~]]	+

OCA at 08:16, 15 April 2020

2020-04-15T08:16:31Z

←Older revision		Revision as of 08:16, 15 April 2020
Line 1:		Line 1:

	==Brugia malayi Trehalose-6 Phosphate Phosphatase in complex with PEG at the active site.==		==Brugia malayi Trehalose-6 Phosphate Phosphatase in complex with PEG at the active site.==
-	<StructureSection load='5e0o' size='340' side='right' caption='[[5e0o]], [[Resolution\|resolution]] 3.00Å' scene=''>	+	<StructureSection load='5e0o' size='340' side='right'caption='[[5e0o]], [[Resolution\|resolution]] 3.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5e0o]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5E0O OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5E0O FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5e0o]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5E0O OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5E0O FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4ofz\|4ofz]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4ofz\|4ofz]]</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Trehalose-phosphatase Trehalose-phosphatase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.3.12 3.1.3.12] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Trehalose-phosphatase Trehalose-phosphatase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.3.12 3.1.3.12] </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=5e0o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5e0o OCA], [http://pdbe.org/5e0o PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5e0o RCSB], [http://www.ebi.ac.uk/pdbsum/5e0o PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5e0o ProSAT]</span></td></tr>	+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5e0o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5e0o OCA], [http://pdbe.org/5e0o PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5e0o RCSB], [http://www.ebi.ac.uk/pdbsum/5e0o PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5e0o ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 24:		Line 24:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Large Structures]]
	[[Category: Trehalose-phosphatase]]		[[Category: Trehalose-phosphatase]]
	[[Category: Agarwal, A]]		[[Category: Agarwal, A]]

OCA at 16:46, 18 August 2017

2017-08-18T16:46:38Z

←Older revision		Revision as of 16:46, 18 August 2017
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 5e0o is ~~ON HOLD~~	+	==Brugia malayi Trehalose-6 Phosphate Phosphatase in complex with PEG at the active site.==
		+	<StructureSection load='5e0o' size='340' side='right' caption='[[5e0o]], [[Resolution\|resolution]] 3.00Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[5e0o]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5E0O OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5E0O FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4ofz\|4ofz]]</td></tr>
		+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Trehalose-phosphatase Trehalose-phosphatase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.3.12 3.1.3.12] </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=5e0o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5e0o OCA], [http://pdbe.org/5e0o PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5e0o RCSB], [http://www.ebi.ac.uk/pdbsum/5e0o PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5e0o ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/GOB1_BRUMA GOB1_BRUMA]] Catalyzes the hydrolysis of trehalose 6-phosphate to trehalose and phosphate (By similarity).
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Parasitic nematodes are responsible for devastating illnesses that plague many of the world's poorest populations indigenous to the tropical areas of developing nations. Among these diseases is lymphatic filariasis, a major cause of permanent and long-term disability. Proteins essential to nematodes that do not have mammalian counterparts represent targets for therapeutic inhibitor discovery. One promising target is trehalose-6-phosphate phosphatase (T6PP) from Brugia malayi. In the model nematode Caenorhabditis elegans, T6PP is essential for survival due to the toxic effect(s) of the accumulation of trehalose 6-phosphate. T6PP has also been shown to be essential in Mycobacterium tuberculosis. We determined the X-ray crystal structure of T6PP from B. malayi. The protein structure revealed a stabilizing N-terminal MIT-like domain and a catalytic C-terminal C2B-type HAD phosphatase fold. Structure-guided mutagenesis, combined with kinetic analyses using a designed competitive inhibitor, trehalose 6-sulfate, identified five residues important for binding and catalysis. This structure-function analysis along with computational mapping provided the basis for the proposed model of the T6PP-trehalose 6-phosphate complex. The model indicates a substrate-binding mode wherein shape complementarity and van der Waals interactions drive recognition. The mode of binding is in sharp contrast to the homolog sucrose-6-phosphate phosphatase where extensive hydrogen-bond interactions are made to the substrate. Together these results suggest that high-affinity inhibitors will be bi-dentate, taking advantage of substrate-like binding to the phosphoryl-binding pocket while simultaneously utilizing non-native binding to the trehalose pocket. The conservation of the key residues that enforce the shape of the substrate pocket in T6PP enzymes suggest that development of broad-range anthelmintic and antibacterial therapeutics employing this platform may be possible.

-	~~Authors: Agarwal~~, A., ~~Misra~~-~~Bhattacharya~~, S., ~~Ravishankar, R~~.	+	Structure of the Trehalose-6-phosphate Phosphatase from Brugia malayi Reveals Key Design Principles for Anthelmintic Drugs.,Farelli JD, Galvin BD, Li Z, Liu C, Aono M, Garland M, Hallett OE, Causey TB, Ali-Reynolds A, Saltzberg DJ, Carlow CK, Dunaway-Mariano D, Allen KN PLoS Pathog. 2014 Jul 3;10(7):e1004245. doi: 10.1371/journal.ppat.1004245., eCollection 2014 Jul. PMID:24992307<ref>PMID:24992307</ref>

-	~~Description: Brugia malayi Trehalose Phosphate Phosphatase in complex with PEG at~~ the ~~active site~~.	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased Structures~~]]	+	</div>
		+	<div class="pdbe-citations 5e0o" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Trehalose-phosphatase]]
	[[Category: Agarwal, A]]		[[Category: Agarwal, A]]
-	[[Category: Ravishankar, R]]
	[[Category: Misra-Bhattacharya, S]]		[[Category: Misra-Bhattacharya, S]]
		+	[[Category: Ravishankar, R]]
		+	[[Category: Complex]]
		+	[[Category: Had]]
		+	[[Category: Hydrolase]]
		+	[[Category: Phosphatase]]

OCA at 04:14, 22 October 2015

2015-10-22T04:14:57Z

←Older revision		Revision as of 04:14, 22 October 2015
Line 3:		Line 3:
	The entry 5e0o is ON HOLD		The entry 5e0o is ON HOLD

-	Authors: Agarwal, A., Bhattacharya, S., Ravishankar, R.	+	Authors: Agarwal, A., Misra-Bhattacharya, S., Ravishankar, R.

-	Description: Brugia malayi Trehalose Phosphate Phosphatase in complex with PEG ~~and SO4~~ at active site.	+	Description: Brugia malayi Trehalose Phosphate Phosphatase in complex with PEG at the active site.
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
-	[[Category: Bhattacharya, S]]
	[[Category: Agarwal, A]]		[[Category: Agarwal, A]]
	[[Category: Ravishankar, R]]		[[Category: Ravishankar, R]]
		+	[[Category: Misra-Bhattacharya, S]]

OCA: Protected "5e0o" [edit=sysop:move=sysop]

2015-10-07T12:47:56Z

Protected "5e0o" [edit=sysop:move=sysop]

←Older revision

Revision as of 12:47, 7 October 2015

OCA: New page: '''Unreleased structure''' The entry 5e0o is ON HOLD Authors: Agarwal, A., Bhattacharya, S., Ravishankar, R. Description: Brugia malayi Trehalose Phosphate Phosphatase in complex with ...

2015-10-07T12:47:54Z

New page: '''Unreleased structure''' The entry 5e0o is ON HOLD Authors: Agarwal, A., Bhattacharya, S., Ravishankar, R. Description: Brugia malayi Trehalose Phosphate Phosphatase in complex with ...

New page

'''Unreleased structure'''

The entry 5e0o is ON HOLD

Authors: Agarwal, A., Bhattacharya, S., Ravishankar, R.

Description: Brugia malayi Trehalose Phosphate Phosphatase in complex with PEG and SO4 at active site.
[[Category: Unreleased Structures]]
[[Category: Bhattacharya, S]]
[[Category: Agarwal, A]]
[[Category: Ravishankar, R]]