6ndl - Revision history

OCA at 06:51, 11 October 2023

OCA — Wed, 11 Oct 2023 06:51:05 GMT

←Older revision		Revision as of 06:51, 11 October 2023
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	<StructureSection load='6ndl' size='340' side='right'caption='[[6ndl]], [[Resolution\|resolution]] 2.00Å' scene=''>		<StructureSection load='6ndl' size='340' side='right'caption='[[6ndl]], [[Resolution\|resolution]] 2.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6ndl]] is a 1 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~9stap 9stap~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6NDL OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6NDL FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6ndl]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Staphylococcus_aureus Staphylococcus aureus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6NDL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6NDL FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BQX:1-[4-(6-aminopurin-9-yl)butylsulfamoyl]-3-[4-[(4~{S})-2-oxidanylidene-1,3,3~{a},4,6,6~{a}-hexahydrothieno[3,4-d]imidazol-4-yl]butyl]urea'>BQX</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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]] 2Å</td></tr>
-	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Biotin--[acetyl-CoA-carboxylase]_ligase Biotin--[acetyl-CoA-carboxylase] ligase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=6.3.4.15 6.3.4.15] </span></td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BQX:1-[4-(6-aminopurin-9-yl)butylsulfamoyl]-3-[4-[(4~{S})-2-oxidanylidene-1,3,3~{a},4,6,6~{a}-hexahydrothieno[3,4-d]imidazol-4-yl]butyl]urea'>BQX</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></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=6ndl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ndl OCA], [~~http~~://pdbe.org/6ndl PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6ndl RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6ndl PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6ndl 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=6ndl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ndl OCA], [https://pdbe.org/6ndl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6ndl RCSB], [https://www.ebi.ac.uk/pdbsum/6ndl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6ndl ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/Q2G258_STAA8 Q2G258_STAA8] Acts both as a biotin--[acetyl-CoA-carboxylase] ligase and a repressor.[HAMAP-Rule:MF_00978]
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
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	</div>		</div>
	<div class="pdbe-citations 6ndl" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 6ndl" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Biotin Protein Ligase 3D structures\|Biotin Protein Ligase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
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	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: ~~Bruning, J B~~]]	+	[[Category: Staphylococcus aureus]]
-	[[Category: ~~Lee, K~~]]	+	[[Category: Bruning JB]]
-	[[Category: ~~Marshall, A C~~]]	+	[[Category: Lee K]]
-	[[Category: ~~Polyak, S W~~]]	+	[[Category: Marshall AC]]
-	[[Category: ~~Amino sulfonylurea]]~~	+	[[Category: Polyak SW]]
-	~~[[Category: Antibiotic]]~~	+
-	~~[[Category: Bpl inhibitor]]~~	+
-	~~[[Category: Ligase]]~~	+
-	~~[[Category: Ligase-ligase inhibitor complex]]~~	+
-	~~[[Category: Sulfonamide analogue~~]]	+

OCA at 13:02, 25 December 2019

OCA — Wed, 25 Dec 2019 13:02:29 GMT

←Older revision		Revision as of 13:02, 25 December 2019
Line 3:		Line 3:
	<StructureSection load='6ndl' size='340' side='right'caption='[[6ndl]], [[Resolution\|resolution]] 2.00Å' scene=''>		<StructureSection load='6ndl' size='340' side='right'caption='[[6ndl]], [[Resolution\|resolution]] 2.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6ndl]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6NDL OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6NDL FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6ndl]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/9stap 9stap]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6NDL OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6NDL FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BQX:1-[4-(6-aminopurin-9-yl)butylsulfamoyl]-3-[4-[(4~{S})-2-oxidanylidene-1,3,3~{a},4,6,6~{a}-hexahydrothieno[3,4-d]imidazol-4-yl]butyl]urea'>BQX</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BQX:1-[4-(6-aminopurin-9-yl)butylsulfamoyl]-3-[4-[(4~{S})-2-oxidanylidene-1,3,3~{a},4,6,6~{a}-hexahydrothieno[3,4-d]imidazol-4-yl]butyl]urea'>BQX</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Biotin--[acetyl-CoA-carboxylase]_ligase Biotin--[acetyl-CoA-carboxylase] ligase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=6.3.4.15 6.3.4.15] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Biotin--[acetyl-CoA-carboxylase]_ligase Biotin--[acetyl-CoA-carboxylase] ligase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=6.3.4.15 6.3.4.15] </span></td></tr>

OCA at 07:43, 18 December 2019

OCA — Wed, 18 Dec 2019 07:43:36 GMT

←Older revision		Revision as of 07:43, 18 December 2019
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-	'''Unreleased structure'''

-	~~The entry~~ 6ndl is ~~ON HOLD until Paper~~ Publication	+	==Crystal structure of Staphylococcus aureus biotin protein ligase in complex with a sulfonamide inhibitor==
		+	<StructureSection load='6ndl' size='340' side='right'caption='[[6ndl]], [[Resolution\|resolution]] 2.00Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[6ndl]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6NDL OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6NDL FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BQX:1-[4-(6-aminopurin-9-yl)butylsulfamoyl]-3-[4-[(4~{S})-2-oxidanylidene-1,3,3~{a},4,6,6~{a}-hexahydrothieno[3,4-d]imidazol-4-yl]butyl]urea'>BQX</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>
		+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Biotin--[acetyl-CoA-carboxylase]_ligase Biotin--[acetyl-CoA-carboxylase] ligase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=6.3.4.15 6.3.4.15] </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=6ndl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ndl OCA], [http://pdbe.org/6ndl PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ndl RCSB], [http://www.ebi.ac.uk/pdbsum/6ndl PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ndl ProSAT]</span></td></tr>
		+	</table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Here, we report the design, synthesis, and evaluation of a series of inhibitors of Staphylococcus aureus BPL (SaBPL), where the central acyl phosphate of the natural intermediate biotinyl-5'-AMP (1) is replaced by a sulfonamide isostere. Acylsulfamide (6) and amino sulfonylurea (7) showed potent in vitro inhibitory activity (Ki = 0.007 +/- 0.003 and 0.065 +/- 0.03 muM, respectively) and antibacterial activity against S. aureus ATCC49775 with minimum inhibitory concentrations of 0.25 and 4 mug/mL, respectively. Additionally, the bimolecular interactions between the BPL and inhibitors 6 and 7 were defined by X-ray crystallography and molecular dynamics simulations. The high acidity of the sulfonamide linkers of 6 and 7 likely contributes to the enhanced in vitro inhibitory activities by promoting interaction with SaBPL Lys187. Analogues with alkylsulfamide (8), beta-ketosulfonamide (9), and beta-hydroxysulfonamide (10) isosteres were devoid of significant activity. Binding free energy estimation using computational methods suggests deprotonated 6 and 7 to be the best binders, which is consistent with enzyme assay results. Compound 6 was unstable in whole blood, leading to poor pharmacokinetics. Importantly, 7 has a vastly improved pharmacokinetic profile compared to that of 6 presumably due to the enhanced metabolic stability of the sulfonamide linker moiety.

-	~~Authors~~:	+	Sulfonamide-Based Inhibitors of Biotin Protein Ligase as New Antibiotic Leads.,Lee KJ, Tieu W, Blanco-Rodriguez B, Paparella AS, Yu J, Hayes A, Feng J, Marshall AC, Noll B, Milne R, Cini D, Wilce MCJ, Booker GW, Bruning JB, Polyak SW, Abell AD ACS Chem Biol. 2019 Sep 20;14(9):1990-1997. doi: 10.1021/acschembio.9b00463. Epub, 2019 Aug 21. PMID:31407891<ref>PMID:31407891</ref>

-	~~Description~~:	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased~~ Structures]]	+	</div>
		+	<div class="pdbe-citations 6ndl" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Bruning, J B]]
		+	[[Category: Lee, K]]
		+	[[Category: Marshall, A C]]
		+	[[Category: Polyak, S W]]
		+	[[Category: Amino sulfonylurea]]
		+	[[Category: Antibiotic]]
		+	[[Category: Bpl inhibitor]]
		+	[[Category: Ligase]]
		+	[[Category: Ligase-ligase inhibitor complex]]
		+	[[Category: Sulfonamide analogue]]

OCA at 05:43, 21 May 2019

OCA — Tue, 21 May 2019 05:43:05 GMT

←Older revision		Revision as of 05:43, 21 May 2019
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 6ndl is ON HOLD	+	The entry 6ndl is ON HOLD until Paper Publication

	Authors:		Authors:

OCA at 04:51, 24 April 2019

OCA — Wed, 24 Apr 2019 04:51:15 GMT

←Older revision		Revision as of 04:51, 24 April 2019
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 6ndl is ON HOLD ~~until Paper Publication~~	+	The entry 6ndl is ON HOLD

	Authors:		Authors:

OCA at 06:29, 30 January 2019

OCA — Wed, 30 Jan 2019 06:29:24 GMT

←Older revision		Revision as of 06:29, 30 January 2019
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 6ndl is ON HOLD	+	The entry 6ndl is ON HOLD until Paper Publication

	Authors:		Authors:

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

OCA — Wed, 19 Dec 2018 06:41:20 GMT

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

←Older revision

Revision as of 06:41, 19 December 2018

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

OCA — Wed, 19 Dec 2018 06:41:18 GMT

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

New page

'''Unreleased structure'''

The entry 6ndl is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]