6upb - Revision history

OCA at 14:57, 13 March 2024

OCA — Wed, 13 Mar 2024 14:57:54 GMT

←Older revision		Revision as of 14:57, 13 March 2024
Line 3:		Line 3:
	<StructureSection load='6upb' size='340' side='right'caption='[[6upb]], [[Resolution\|resolution]] 1.89Å' scene=''>		<StructureSection load='6upb' size='340' side='right'caption='[[6upb]], [[Resolution\|resolution]] 1.89Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6upb]] is a 2 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~Salts Salts~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6UPB OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=6UPB FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6upb]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Salmonella_enterica_subsp._enterica_serovar_Typhimurium_str._SL1344 Salmonella enterica subsp. enterica serovar Typhimurium str. SL1344]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6UPB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6UPB FirstGlance]. <br>
-	</td></tr><tr id='~~gene~~'><td class="sblockLbl"><b>[[~~Gene~~\|~~Gene~~:]]</b></td><td class="sblockDat"~~>otsB, SL1344_1863 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&~~id~~=216597 SALTS])</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]] 1.89Å</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=6upb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6upb OCA], [https://pdbe.org/6upb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6upb RCSB], [https://www.ebi.ac.uk/pdbsum/6upb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6upb 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=6upb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6upb OCA], [~~http~~://pdbe.org/6upb PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6upb RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6upb PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6upb ProSAT]</span></td></tr>	+
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/OTSB_SALTS OTSB_SALTS]] Removes the phosphate from trehalose 6-phosphate to produce free trehalose.	+	[https://www.uniprot.org/uniprot/OTSB_SALTS OTSB_SALTS] Removes the phosphate from trehalose 6-phosphate to produce free trehalose.
-	~~<div style="background-color:#fffaf0;">~~	+
-	~~== Publication Abstract from PubMed ==~~	+
-	Trehalose-6-phosphate phosphatase (T6PP) catalyzes the dephosphorylation of trehalose 6-phosphate (T6P) to the disaccharide trehalose. The enzyme is not present in mammals but is essential to the viability of multiple lower organisms as trehalose is a critical metabolite, and T6P accumulation is toxic. Hence, T6PP is a target for therapeutics of human pathologies caused by bacteria, fungi, and parasitic nematodes. Here, we report the X-ray crystal structures of Salmonella typhimurium T6PP (StT6PP) in its apo form and in complex with the cofactor Mg(2+) and the substrate analogue trehalose 6-sulfate (T6S), the product trehalose, or the competitive inhibitor 4-n-octylphenyl alpha-d-glucopyranoside 6-sulfate (OGS). OGS replaces the substrate phosphoryl group with a sulfate group and the glucosyl ring distal to the sulfate group with an octylphenyl moiety. The structures of these substrate-analogue and product complexes with T6PP show that specificity is conferred via hydrogen bonds to the glucosyl group proximal to the phosphoryl moiety through Glu123, Lys125, and Glu167, conserved in T6PPs from multiple species. The structure of the first-generation inhibitor OGS shows that it retains the substrate-binding interactions observed for the sulfate group and the proximal glucosyl ring. The OGS octylphenyl moiety binds in a unique manner, indicating that this subsite can tolerate various chemotypes. Together, these findings show that these conserved interactions at the proximal glucosyl ring binding site could provide the basis for the development of broad-spectrum therapeutics, whereas variable interactions at the divergent distal subsite could present an opportunity for the design of potent organism-specific therapeutics.	+
-		+
-	Structural Analysis of Binding Determinants of Salmonella typhimurium Trehalose-6-phosphate Phosphatase Using Ground-State Complexes.,Harvey CM, O'Toole KH, Liu C, Mariano P, Dunaway-Mariano D, Allen KN Biochemistry. 2020 Aug 17. doi: 10.1021/acs.biochem.0c00317. PMID:32786412<ref>PMID:32786412</ref>	+
-		+
-	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~	+
-	~~</div>~~	+
-	~~<div class="pdbe-citations 6upb" style="background-color:#fffaf0;"></div>~~	+
-	~~== References ==~~	+
-	~~<references/>~~	+
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: ~~Salts]]~~	+	[[Category: Salmonella enterica subsp. enterica serovar Typhimurium str. SL1344]]
-	~~[[Category: Trehalose-phosphatase~~]]	+	[[Category: Allen KN]]
-	[[Category: Allen~~, K N~~]]	+	[[Category: Harvey CM]]
-	[[Category: Harvey~~, C M]]~~	+
-	~~[[Category: Had superfamily]]~~	+
-	~~[[Category: Hydrolase]]~~	+
-	~~[[Category: Rossmann fold]]~~	+
-	~~[[Category: Sugar binding~~]]	+

OCA at 11:26, 23 September 2020

OCA — Wed, 23 Sep 2020 11:26:42 GMT

←Older revision		Revision as of 11:26, 23 September 2020
Line 1:		Line 1:

	==Structure of apo trehalose-6-phosphate phosphatase from Salmonella typhimurium==		==Structure of apo trehalose-6-phosphate phosphatase from Salmonella typhimurium==
-	<StructureSection load='6upb' size='340' side='right'caption='[[6upb]]' scene=''>	+	<StructureSection load='6upb' size='340' side='right'caption='[[6upb]], [[Resolution\|resolution]] 1.89Å' 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=6UPB OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6UPB FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6upb]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Salts Salts]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6UPB OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6UPB FirstGlance]. <br>
-	</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=6upb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6upb OCA], [http://pdbe.org/6upb PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6upb RCSB], [http://www.ebi.ac.uk/pdbsum/6upb PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6upb ProSAT]</span></td></tr>	+	</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">otsB, SL1344_1863 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=216597 SALTS])</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://proteopedia.org/fgij/fg.htm?mol=6upb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6upb OCA], [http://pdbe.org/6upb PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6upb RCSB], [http://www.ebi.ac.uk/pdbsum/6upb PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6upb ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/OTSB_SALTS OTSB_SALTS]] Removes the phosphate from trehalose 6-phosphate to produce free trehalose.
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Trehalose-6-phosphate phosphatase (T6PP) catalyzes the dephosphorylation of trehalose 6-phosphate (T6P) to the disaccharide trehalose. The enzyme is not present in mammals but is essential to the viability of multiple lower organisms as trehalose is a critical metabolite, and T6P accumulation is toxic. Hence, T6PP is a target for therapeutics of human pathologies caused by bacteria, fungi, and parasitic nematodes. Here, we report the X-ray crystal structures of Salmonella typhimurium T6PP (StT6PP) in its apo form and in complex with the cofactor Mg(2+) and the substrate analogue trehalose 6-sulfate (T6S), the product trehalose, or the competitive inhibitor 4-n-octylphenyl alpha-d-glucopyranoside 6-sulfate (OGS). OGS replaces the substrate phosphoryl group with a sulfate group and the glucosyl ring distal to the sulfate group with an octylphenyl moiety. The structures of these substrate-analogue and product complexes with T6PP show that specificity is conferred via hydrogen bonds to the glucosyl group proximal to the phosphoryl moiety through Glu123, Lys125, and Glu167, conserved in T6PPs from multiple species. The structure of the first-generation inhibitor OGS shows that it retains the substrate-binding interactions observed for the sulfate group and the proximal glucosyl ring. The OGS octylphenyl moiety binds in a unique manner, indicating that this subsite can tolerate various chemotypes. Together, these findings show that these conserved interactions at the proximal glucosyl ring binding site could provide the basis for the development of broad-spectrum therapeutics, whereas variable interactions at the divergent distal subsite could present an opportunity for the design of potent organism-specific therapeutics.
		+
		+	Structural Analysis of Binding Determinants of Salmonella typhimurium Trehalose-6-phosphate Phosphatase Using Ground-State Complexes.,Harvey CM, O'Toole KH, Liu C, Mariano P, Dunaway-Mariano D, Allen KN Biochemistry. 2020 Aug 17. doi: 10.1021/acs.biochem.0c00317. PMID:32786412<ref>PMID:32786412</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 6upb" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Allen KN]]	+	[[Category: Salts]]
-	[[Category: Harvey CM]]	+	[[Category: Trehalose-phosphatase]]
		+	[[Category: Allen, K N]]
		+	[[Category: Harvey, C M]]
		+	[[Category: Had superfamily]]
		+	[[Category: Hydrolase]]
		+	[[Category: Rossmann fold]]
		+	[[Category: Sugar binding]]

OCA at 11:15, 26 August 2020

OCA — Wed, 26 Aug 2020 11:15:22 GMT

←Older revision		Revision as of 11:15, 26 August 2020
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 6upb ~~is ON HOLD until Paper Publication~~	+	==Structure of apo trehalose-6-phosphate phosphatase from Salmonella typhimurium==
-		+	<StructureSection load='6upb' size='340' side='right'caption='[[6upb]]' scene=''>
-	~~Authors~~:	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6UPB OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6UPB FirstGlance]. <br>
-	~~Description~~:	+	</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=6upb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6upb OCA], [http://pdbe.org/6upb PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6upb RCSB], [http://www.ebi.ac.uk/pdbsum/6upb PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6upb ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	</table>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Allen KN]]
		+	[[Category: Harvey CM]]

OCA at 05:58, 18 December 2019

OCA — Wed, 18 Dec 2019 05:58:14 GMT

←Older revision		Revision as of 05:58, 18 December 2019
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 6upb is ON HOLD until ~~Dec 12 2020~~	+	The entry 6upb is ON HOLD until Paper Publication

	Authors:		Authors:

OCA at 13:51, 20 November 2019

OCA — Wed, 20 Nov 2019 13:51:59 GMT

←Older revision		Revision as of 13:51, 20 November 2019
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 6upb is ON HOLD	+	The entry 6upb is ON HOLD until Dec 12 2020

	Authors:		Authors:

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

OCA — Wed, 23 Oct 2019 05:19:05 GMT

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

←Older revision

Revision as of 05:19, 23 October 2019

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

OCA — Wed, 23 Oct 2019 05:19:03 GMT

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

New page

'''Unreleased structure'''

The entry 6upb is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]