7luh - Revision history

OCA at 15:59, 18 October 2023

2023-10-18T15:59:54Z

←Older revision		Revision as of 15:59, 18 October 2023
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	<StructureSection load='7luh' size='340' side='right'caption='[[7luh]], [[Resolution\|resolution]] 1.84Å' scene=''>		<StructureSection load='7luh' size='340' side='right'caption='[[7luh]], [[Resolution\|resolution]] 1.84Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[7luh]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7LUH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7LUH FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7luh]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Burkholderia_pseudomallei_K96243 Burkholderia pseudomallei K96243]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7LUH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7LUH FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=YCS:(2~{R})-2-(4-bromanylphenoxy)propanamide'>YCS</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]] 1.84Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=YCS:(2~{R})-2-(4-bromanylphenoxy)propanamide'>YCS</scene></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=7luh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7luh OCA], [https://pdbe.org/7luh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7luh RCSB], [https://www.ebi.ac.uk/pdbsum/7luh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7luh 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=7luh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7luh OCA], [https://pdbe.org/7luh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7luh RCSB], [https://www.ebi.ac.uk/pdbsum/7luh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7luh ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/Q63Y08_BURPS Q63Y08_BURPS]
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 20:		Line 23:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Burkholderia pseudomallei K96243]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Martin~~, J L~~]]	+	[[Category: Martin JL]]
-	[[Category: McMahon~~, R M~~]]	+	[[Category: McMahon RM]]
-	[[Category: Petit~~, G A]]~~	+	[[Category: Petit GA]]
-	~~[[Category: Bpsdsba]]~~	+
-	~~[[Category: Cryptic-pocket]]~~	+
-	~~[[Category: Fragment]]~~	+
-	~~[[Category: Oxidoreductase~~]]	+

OCA at 10:03, 12 January 2022

2022-01-12T10:03:59Z

←Older revision		Revision as of 10:03, 12 January 2022
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	==Burkholderia pseudomallei Disulfide bond forming protein A (DsbA) liganded with fragment bromophenoxy propanamide==		==Burkholderia pseudomallei Disulfide bond forming protein A (DsbA) liganded with fragment bromophenoxy propanamide==
-	<StructureSection load='7luh' size='340' side='right'caption='[[7luh]]' scene=''>	+	<StructureSection load='7luh' size='340' side='right'caption='[[7luh]], [[Resolution\|resolution]] 1.84Å' 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=7LUH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7LUH FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7luh]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7LUH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7LUH 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=7luh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7luh OCA], [https://pdbe.org/7luh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7luh RCSB], [https://www.ebi.ac.uk/pdbsum/7luh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7luh 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=YCS:(2~{R})-2-(4-bromanylphenoxy)propanamide'>YCS</scene></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=7luh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7luh OCA], [https://pdbe.org/7luh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7luh RCSB], [https://www.ebi.ac.uk/pdbsum/7luh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7luh ProSAT]</span></td></tr>
	</table>		</table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Disulfide-bond-forming proteins (Dsbs) play a crucial role in the pathogenicity of many Gram-negative bacteria. Disulfide-bond-forming protein A (DsbA) catalyzes the formation of the disulfide bonds necessary for the activity and stability of multiple substrate proteins, including many virulence factors. Hence, DsbA is an attractive target for the development of new drugs to combat bacterial infections. Here, two fragments, bromophenoxy propanamide (1) and 4-methoxy-N-phenylbenzenesulfonamide (2), were identified that bind to DsbA from the pathogenic bacterium Burkholderia pseudomallei, the causative agent of melioidosis. The crystal structures of oxidized B. pseudomallei DsbA (termed BpsDsbA) co-crystallized with 1 or 2 show that both fragments bind to a hydrophobic pocket that is formed by a change in the side-chain orientation of Tyr110. This conformational change opens a `cryptic' pocket that is not evident in the apoprotein structure. This binding location was supported by 2D-NMR studies, which identified a chemical shift perturbation of the Tyr110 backbone amide resonance of more than 0.05 p.p.m. upon the addition of 2 mM fragment 1 and of more than 0.04 p.p.m. upon the addition of 1 mM fragment 2. Although binding was detected by both X-ray crystallography and NMR, the binding affinity (Kd) for both fragments was low (above 2 mM), suggesting weak interactions with BpsDsbA. This conclusion is also supported by the crystal structure models, which ascribe partial occupancy to the ligands in the cryptic binding pocket. Small fragments such as 1 and 2 are not expected to have a high energetic binding affinity due to their relatively small surface area and the few functional groups that are available for intermolecular interactions. However, their simplicity makes them ideal for functionalization and optimization. The identification of the binding sites of 1 and 2 to BpsDsbA could provide a starting point for the development of more potent novel antimicrobial compounds that target DsbA and bacterial virulence.
		+
		+	Identification and characterization of two drug-like fragments that bind to the same cryptic binding pocket of Burkholderia pseudomallei DsbA.,Petit GA, Mohanty B, McMahon RM, Nebl S, Hilko DH, Wilde KL, Scanlon MJ, Martin JL, Halili MA Acta Crystallogr D Struct Biol. 2022 Jan 1;78(Pt 1):75-90. doi:, 10.1107/S2059798321011475. Epub 2022 Jan 1. PMID:34981764<ref>PMID:34981764</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7luh" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Martin JL]]	+	[[Category: Martin, J L]]
-	[[Category: McMahon RM]]	+	[[Category: McMahon, R M]]
-	[[Category: Petit GA]]	+	[[Category: Petit, G A]]
		+	[[Category: Bpsdsba]]
		+	[[Category: Cryptic-pocket]]
		+	[[Category: Fragment]]
		+	[[Category: Oxidoreductase]]

OCA at 10:40, 5 January 2022

2022-01-05T10:40:15Z

←Older revision		Revision as of 10:40, 5 January 2022
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-	'''Unreleased structure'''

-	~~The entry~~ 7luh ~~is ON HOLD until Paper Publication~~	+	==Burkholderia pseudomallei Disulfide bond forming protein A (DsbA) liganded with fragment bromophenoxy propanamide==
-		+	<StructureSection load='7luh' size='340' side='right'caption='[[7luh]]' scene=''>
-	~~Authors~~: ~~Petit~~, G.A., ~~Martin~~, J.L., ~~McMahon~~, R.M.	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7LUH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7LUH FirstGlance]. <br>
-	~~Description: Burkholderia pseudomallei Disulfide bond forming protein A (DsbA) liganded with fragment bromophenoxy propanamide~~	+	</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=7luh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7luh OCA], [https://pdbe.org/7luh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7luh RCSB], [https://www.ebi.ac.uk/pdbsum/7luh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7luh ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	</table>
-	[[Category: ~~Mcmahon, R.M~~]]	+	__TOC__
-	[[Category: ~~Martin, J.L~~]]	+	</StructureSection>
-	[[Category: Petit~~, G.A~~]]	+	[[Category: Large Structures]]
		+	[[Category: Martin JL]]
		+	[[Category: McMahon RM]]
		+	[[Category: Petit GA]]

OCA at 12:37, 3 November 2021

2021-11-03T12:37:33Z

←Older revision		Revision as of 12:37, 3 November 2021
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

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

	Authors: Petit, G.A., Martin, J.L., McMahon, R.M.		Authors: Petit, G.A., Martin, J.L., McMahon, R.M.

OCA at 04:02, 6 October 2021

2021-10-06T04:02:42Z

←Older revision		Revision as of 04:02, 6 October 2021
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 7luh is ON HOLD ~~until Paper Publication~~	+	The entry 7luh is ON HOLD

	Authors: Petit, G.A., Martin, J.L., McMahon, R.M.		Authors: Petit, G.A., Martin, J.L., McMahon, R.M.

OCA at 06:11, 21 April 2021

2021-04-21T06:11:39Z

←Older revision		Revision as of 06:11, 21 April 2021
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

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

	Authors: Petit, G.A., Martin, J.L., McMahon, R.M.		Authors: Petit, G.A., Martin, J.L., McMahon, R.M.
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	Description: Burkholderia pseudomallei Disulfide bond forming protein A (DsbA) liganded with fragment bromophenoxy propanamide		Description: Burkholderia pseudomallei Disulfide bond forming protein A (DsbA) liganded with fragment bromophenoxy propanamide
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
-	[[Category: Petit, G.A]]
	[[Category: Mcmahon, R.M]]		[[Category: Mcmahon, R.M]]
	[[Category: Martin, J.L]]		[[Category: Martin, J.L]]
		+	[[Category: Petit, G.A]]

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

2021-03-03T13:26:35Z

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

←Older revision

Revision as of 13:26, 3 March 2021

OCA: New page: '''Unreleased structure''' The entry 7luh is ON HOLD Authors: Petit, G.A., Martin, J.L., McMahon, R.M. Description: Burkholderia pseudomallei Disulfide bond forming protein A (DsbA) li...

2021-03-03T13:26:34Z

New page: '''Unreleased structure''' The entry 7luh is ON HOLD Authors: Petit, G.A., Martin, J.L., McMahon, R.M. Description: Burkholderia pseudomallei Disulfide bond forming protein A (DsbA) li...

New page

'''Unreleased structure'''

The entry 7luh is ON HOLD

Authors: Petit, G.A., Martin, J.L., McMahon, R.M.

Description: Burkholderia pseudomallei Disulfide bond forming protein A (DsbA) liganded with fragment bromophenoxy propanamide
[[Category: Unreleased Structures]]
[[Category: Petit, G.A]]
[[Category: Mcmahon, R.M]]
[[Category: Martin, J.L]]