5i8w - Revision history

OCA at 08:27, 23 August 2023

OCA — Wed, 23 Aug 2023 08:27:06 GMT

←Older revision		Revision as of 08:27, 23 August 2023
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	<StructureSection load='5i8w' size='340' side='right'caption='[[5i8w]], [[Resolution\|resolution]] 1.63Å' scene=''>		<StructureSection load='5i8w' size='340' side='right'caption='[[5i8w]], [[Resolution\|resolution]] 1.63Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5i8w]] is a 1 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~"bacillus_pseudomallei"_whitmore_1913 "bacillus~~ pseudomallei~~" whitmore 1913~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5I8W OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=5I8W FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5i8w]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Burkholderia_pseudomallei Burkholderia pseudomallei]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5I8W OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5I8W FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat" id="~~ligandDat~~">~~<scene name='pdbligand=69H:4~~-~~FLUORO-5-HEXYL-2-(2-METHYLPHENOXY)PHENOL'>69H</scene>~~, ~~<scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</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]] 1.629Å</td></tr>
-	<tr id='~~gene~~'><td class="sblockLbl"><b>[[~~Gene~~\|~~Gene~~:]]</b></td><td class="sblockDat">fabI, fabI_2, ACT79_25590, AM256_11615, AM257_11635, AMS56_08605, DP46_2957, DP49_6839, ERS012314_03793, ERS012372_03823, SY87_14645, TR70_1075, VU09_13745 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=~~28450~~ "~~Bacillus pseudomallei~~" ~~Whitmore 1913])</td~~><~~/tr>~~	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=69H:4-FLUORO-5-HEXYL-2-(2-METHYLPHENOXY)PHENOL'>69H</scene>, <scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene></td></tr>
-	~~<tr id~~='~~activity'><td class~~=~~"sblockLbl"><b>Activity~~:~~</b~~></td><~~td class~~=~~"sblockDat"><span class~~=~~'plainlinks'>[http~~:~~//en.wikipedia.org/wiki/Enoyl~~-~~[acyl~~-~~carrier-protein]_reductase_(NADH) Enoyl-[acyl-carrier-protein] reductase (NADH)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.3.1.9 1.3.1.9]~~ </~~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=5i8w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5i8w OCA], [https://pdbe.org/5i8w PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5i8w RCSB], [https://www.ebi.ac.uk/pdbsum/5i8w PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5i8w 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=5i8w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5i8w OCA], [~~http~~://pdbe.org/5i8w PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5i8w RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5i8w PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5i8w ProSAT]</span></td></tr>	+
	</table>		</table>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/A0A0H3HP34_BURP2 A0A0H3HP34_BURP2]
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: Bacillus pseudomallei whitmore 1913]]
-	[[Category: Large Structures]]
-	[[Category: Eltschkner, S]]
-	[[Category: Hirschbeck, M W]]
-	[[Category: Kisker, C]]
-	[[Category: Tonge, P J]]
	[[Category: Burkholderia pseudomallei]]		[[Category: Burkholderia pseudomallei]]
-	[[Category: ~~Diphenyl ether~~]]	+	[[Category: Large Structures]]
-	[[Category: ~~Enoyl-acp reductase~~]]	+	[[Category: Eltschkner S]]
-	[[Category: ~~Oxidoreductase~~]]	+	[[Category: Hirschbeck MW]]
-	[[Category: ~~Slow-binding inhibitor~~]]	+	[[Category: Kisker C]]
		+	[[Category: Tonge PJ]]

OCA at 07:09, 3 June 2020

OCA — Wed, 03 Jun 2020 07:09:02 GMT

←Older revision		Revision as of 07:09, 3 June 2020
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	==Crystal structure of B. pseudomallei FabI in complex with NAD and PT401==		==Crystal structure of B. pseudomallei FabI in complex with NAD and PT401==
-	<StructureSection load='5i8w' size='340' side='right' caption='[[5i8w]], [[Resolution\|resolution]] 1.63Å' scene=''>	+	<StructureSection load='5i8w' size='340' side='right'caption='[[5i8w]], [[Resolution\|resolution]] 1.63Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5i8w]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5I8W OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5I8W FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5i8w]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_pseudomallei"_whitmore_1913 "bacillus pseudomallei" whitmore 1913]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5I8W OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5I8W FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=69H:4-FLUORO-5-HEXYL-2-(2-METHYLPHENOXY)PHENOL'>69H</scene>, <scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=69H:4-FLUORO-5-HEXYL-2-(2-METHYLPHENOXY)PHENOL'>69H</scene>, <scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">fabI, fabI_2, ACT79_25590, AM256_11615, AM257_11635, AMS56_08605, DP46_2957, DP49_6839, ERS012314_03793, ERS012372_03823, SY87_14645, TR70_1075, VU09_13745 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=28450 "Bacillus pseudomallei" Whitmore 1913])</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Enoyl-[acyl-carrier-protein]_reductase_(NADH) Enoyl-[acyl-carrier-protein] reductase (NADH)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.3.1.9 1.3.1.9] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Enoyl-[acyl-carrier-protein]_reductase_(NADH) Enoyl-[acyl-carrier-protein] reductase (NADH)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.3.1.9 1.3.1.9] </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=5i8w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5i8w OCA], [http://pdbe.org/5i8w PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5i8w RCSB], [http://www.ebi.ac.uk/pdbsum/5i8w PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5i8w 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=5i8w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5i8w OCA], [http://pdbe.org/5i8w PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5i8w RCSB], [http://www.ebi.ac.uk/pdbsum/5i8w PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5i8w ProSAT]</span></td></tr>
	</table>		</table>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
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	</div>		</div>
	<div class="pdbe-citations 5i8w" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5i8w" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Enoyl-Acyl-Carrier Protein Reductase 3D structures\|Enoyl-Acyl-Carrier Protein Reductase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Bacillus pseudomallei whitmore 1913]]
		+	[[Category: Large Structures]]
	[[Category: Eltschkner, S]]		[[Category: Eltschkner, S]]
	[[Category: Hirschbeck, M W]]		[[Category: Hirschbeck, M W]]

OCA at 08:08, 9 March 2017

OCA — Thu, 09 Mar 2017 08:08:40 GMT

←Older revision		Revision as of 08:08, 9 March 2017
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 5i8w is ~~ON HOLD until Paper~~ Publication	+	==Crystal structure of B. pseudomallei FabI in complex with NAD and PT401==
		+	<StructureSection load='5i8w' size='340' side='right' caption='[[5i8w]], [[Resolution\|resolution]] 1.63Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[5i8w]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5I8W OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5I8W FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=69H:4-FLUORO-5-HEXYL-2-(2-METHYLPHENOXY)PHENOL'>69H</scene>, <scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene></td></tr>
		+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Enoyl-[acyl-carrier-protein]_reductase_(NADH) Enoyl-[acyl-carrier-protein] reductase (NADH)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.3.1.9 1.3.1.9] </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=5i8w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5i8w OCA], [http://pdbe.org/5i8w PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5i8w RCSB], [http://www.ebi.ac.uk/pdbsum/5i8w PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5i8w ProSAT]</span></td></tr>
		+	</table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	There is growing awareness of the link between drug-target residence time and in vivo drug activity, and there are increasing efforts to determine the molecular factors that control the lifetime of a drug-target complex. Rational alterations in drug-target residence time require knowledge of both the ground and transition states on the inhibition reaction coordinate, and we have determined the structure-kinetic relationship for 22 ethyl or hexyl substituted diphenyl ethers that are slow-binding inhibitors of bpFabI1, the enoyl-ACP reductase FabI1 from Burkholderia pseudomallei. Analysis of enzyme inhibition using a 2D-kinetic map demonstrates that the ethyl and hexyl diphenyl ethers fall into two distinct clusters. Modifications to the ethyl diphenyl ether B ring result in changes to both on and off-rates, where residence times of up to ~700 min (~11 h) are achieved by either ground state stabilization (PT444) or transition state destabilization (slower on-rate) (PT404). By contrast, modifications to the hexyl diphenyl ether B ring result in residence times of 300 min (~5 h) through changes in only ground state stabilization (PT119). Structural analysis of 9 enzyme:inhibitor complexes reveal that the variation in structure-kinetic relationships can be rationalized by structural rearrangements of bpFabI1 and subtle changes to the orientation of the inhibitor in the binding pocket. Finally, we demonstrate that three compounds with residence times on bpFabI1 of between 118 min (~2 h) and 670 min (~11 h) have in vivo efficacy in an acute B. pseudomallei murine infection model using the virulent B. pseudomallei strain Bp400.

-	~~Authors~~:	+	Rational Optimization of Diphenyl Ether Binding Kinetics to the Enoyl-ACP Reductase FabI1 from Burkholderia pseudomallei.,Neckles CM, Eltschkner S, Cummings JE, Hirschbeck M, Daryaee F, Bommineni GR, Zhang Z, Spagnuolo LA, Yu W, Davoodi S, Slayden RA, Kisker C, Tonge PJ Biochemistry. 2017 Feb 22. doi: 10.1021/acs.biochem.6b01048. PMID:28225601<ref>PMID:28225601</ref>

-	~~Description~~:	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased Structures~~]]	+	</div>
		+	<div class="pdbe-citations 5i8w" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Eltschkner, S]]
		+	[[Category: Hirschbeck, M W]]
		+	[[Category: Kisker, C]]
		+	[[Category: Tonge, P J]]
		+	[[Category: Burkholderia pseudomallei]]
		+	[[Category: Diphenyl ether]]
		+	[[Category: Enoyl-acp reductase]]
		+	[[Category: Oxidoreductase]]
		+	[[Category: Slow-binding inhibitor]]

OCA at 14:14, 15 May 2016

OCA — Sun, 15 May 2016 14:14:56 GMT

←Older revision		Revision as of 14:14, 15 May 2016
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	The entry 5i8w is ON HOLD until Paper Publication		The entry 5i8w is ON HOLD until Paper Publication

-	Authors: ~~Hirschbeck, M.W., Eltschkner, S., Tonge, P.J., Kisker, C.~~	+	Authors:

	Description:		Description:
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
-	[[Category: Hirschbeck, M.W]]
-	[[Category: Kisker, C]]
-	[[Category: Eltschkner, S]]
-	[[Category: Tonge, P.J]]

OCA at 00:18, 11 May 2016

OCA — Wed, 11 May 2016 00:18:00 GMT

←Older revision		Revision as of 00:18, 11 May 2016
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 5i8w is ON HOLD	+	The entry 5i8w is ON HOLD until Paper Publication

	Authors: Hirschbeck, M.W., Eltschkner, S., Tonge, P.J., Kisker, C.		Authors: Hirschbeck, M.W., Eltschkner, S., Tonge, P.J., Kisker, C.

OCA: Protected "5i8w" [edit=sysop:move=sysop]

OCA — Wed, 02 Mar 2016 13:32:46 GMT

Protected "5i8w" [edit=sysop:move=sysop]

←Older revision

Revision as of 13:32, 2 March 2016

OCA: New page: '''Unreleased structure''' The entry 5i8w is ON HOLD Authors: Hirschbeck, M.W., Eltschkner, S., Tonge, P.J., Kisker, C. Description: Category: Unreleased Structures [[Category: Hi...

OCA — Wed, 02 Mar 2016 13:32:43 GMT

New page: '''Unreleased structure''' The entry 5i8w is ON HOLD Authors: Hirschbeck, M.W., Eltschkner, S., Tonge, P.J., Kisker, C. Description: Category: Unreleased Structures [[Category: Hi...

New page

'''Unreleased structure'''

The entry 5i8w is ON HOLD

Authors: Hirschbeck, M.W., Eltschkner, S., Tonge, P.J., Kisker, C.

Description:
[[Category: Unreleased Structures]]
[[Category: Hirschbeck, M.W]]
[[Category: Kisker, C]]
[[Category: Eltschkner, S]]
[[Category: Tonge, P.J]]