5z9l - Revision history

OCA at 08:50, 22 November 2023

OCA — Wed, 22 Nov 2023 08:50:16 GMT

←Older revision		Revision as of 08:50, 22 November 2023
Line 3:		Line 3:
	<StructureSection load='5z9l' size='340' side='right'caption='[[5z9l]], [[Resolution\|resolution]] 1.60Å' scene=''>		<StructureSection load='5z9l' size='340' side='right'caption='[[5z9l]], [[Resolution\|resolution]] 1.60Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5z9l]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5Z9L OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=5Z9L FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5z9l]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli_K-12 Escherichia coli K-12]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5Z9L OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5Z9L FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=8H8:2-FLUORO-4-HYDROXYBENZONITRILE'>8H8</scene>, <scene name='pdbligand=AX7:1H-BENZIMIDAZOL-2-AMINE'>AX7</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</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]] 1.6Å</td></tr>
-	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/DNA_topoisomerase_(ATP-hydrolyzing) DNA topoisomerase (ATP-hydrolyzing)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=5.99.1.3 5.99.1.3] </span></td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=8H8:2-FLUORO-4-HYDROXYBENZONITRILE'>8H8</scene>, <scene name='pdbligand=AX7:1H-BENZIMIDAZOL-2-AMINE'>AX7</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></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=5z9l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5z9l OCA], [~~http~~://pdbe.org/5z9l PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5z9l RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5z9l PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5z9l 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=5z9l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5z9l OCA], [https://pdbe.org/5z9l PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5z9l RCSB], [https://www.ebi.ac.uk/pdbsum/5z9l PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5z9l ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/GYRB_ECOLI GYRB_ECOLI]] DNA gyrase negatively supercoils closed circular double-stranded DNA in an ATP-dependent manner and also catalyzes the interconversion of other topological isomers of double-stranded DNA rings, including catenanes and knotted rings.<ref>PMID:12051843</ref> <ref>PMID:18642932</ref> <ref>PMID:20675723</ref>	+	[https://www.uniprot.org/uniprot/GYRB_ECOLI GYRB_ECOLI] DNA gyrase negatively supercoils closed circular double-stranded DNA in an ATP-dependent manner and also catalyzes the interconversion of other topological isomers of double-stranded DNA rings, including catenanes and knotted rings.<ref>PMID:12051843</ref> <ref>PMID:18642932</ref> <ref>PMID:20675723</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 22:		Line 22:
	==See Also==		==See Also==
	*[[Gyrase 3D Structures\|Gyrase 3D Structures]]		*[[Gyrase 3D Structures\|Gyrase 3D Structures]]
-	*[[Topoisomerase 3D structures\|Topoisomerase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Escherichia coli K-12]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Huang, X]]	+	[[Category: Huang X]]
-	[[Category: Zhou, H]]	+	[[Category: Zhou H]]
-	~~[[Category: Antibacterial]]~~	+
-	~~[[Category: Dna topoisomerase]]~~	+
-	~~[[Category: Drug target]]~~	+
-	~~[[Category: Fragment-base lead discovery]]~~	+
-	~~[[Category: Isomerase~~]]	+

OCA at 21:16, 28 October 2020

OCA — Wed, 28 Oct 2020 21:16:52 GMT

←Older revision		Revision as of 21:16, 28 October 2020
Line 1:		Line 1:

	==Bacterial GyrB ATPase domain in complex with a chemical fragment==		==Bacterial GyrB ATPase domain in complex with a chemical fragment==
-	<StructureSection load='5z9l' size='340' side='right' caption='[[5z9l]], [[Resolution\|resolution]] 1.60Å' scene=''>	+	<StructureSection load='5z9l' size='340' side='right'caption='[[5z9l]], [[Resolution\|resolution]] 1.60Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5z9l]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5Z9L OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5Z9L FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5z9l]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5Z9L OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5Z9L FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=8H8:2-FLUORO-4-HYDROXYBENZONITRILE'>8H8</scene>, <scene name='pdbligand=AX7:1H-BENZIMIDAZOL-2-AMINE'>AX7</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=8H8:2-FLUORO-4-HYDROXYBENZONITRILE'>8H8</scene>, <scene name='pdbligand=AX7:1H-BENZIMIDAZOL-2-AMINE'>AX7</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/DNA_topoisomerase_(ATP-hydrolyzing) DNA topoisomerase (ATP-hydrolyzing)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=5.99.1.3 5.99.1.3] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/DNA_topoisomerase_(ATP-hydrolyzing) DNA topoisomerase (ATP-hydrolyzing)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=5.99.1.3 5.99.1.3] </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=5z9l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5z9l OCA], [http://pdbe.org/5z9l PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5z9l RCSB], [http://www.ebi.ac.uk/pdbsum/5z9l PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5z9l 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=5z9l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5z9l OCA], [http://pdbe.org/5z9l PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5z9l RCSB], [http://www.ebi.ac.uk/pdbsum/5z9l PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5z9l ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 19:		Line 19:
	</div>		</div>
	<div class="pdbe-citations 5z9l" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5z9l" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Gyrase 3D Structures\|Gyrase 3D Structures]]
		+	*[[Topoisomerase 3D structures\|Topoisomerase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Large Structures]]
	[[Category: Huang, X]]		[[Category: Huang, X]]
	[[Category: Zhou, H]]		[[Category: Zhou, H]]

OCA at 06:40, 12 December 2018

OCA — Wed, 12 Dec 2018 06:40:28 GMT

←Older revision		Revision as of 06:40, 12 December 2018
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 5z9l is ~~ON HOLD~~ ~~until Paper~~ Publication	+	==Bacterial GyrB ATPase domain in complex with a chemical fragment==
		+	<StructureSection load='5z9l' size='340' side='right' caption='[[5z9l]], [[Resolution\|resolution]] 1.60Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[5z9l]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5Z9L OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5Z9L FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=8H8:2-FLUORO-4-HYDROXYBENZONITRILE'>8H8</scene>, <scene name='pdbligand=AX7:1H-BENZIMIDAZOL-2-AMINE'>AX7</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr>
		+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/DNA_topoisomerase_(ATP-hydrolyzing) DNA topoisomerase (ATP-hydrolyzing)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=5.99.1.3 5.99.1.3] </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=5z9l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5z9l OCA], [http://pdbe.org/5z9l PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5z9l RCSB], [http://www.ebi.ac.uk/pdbsum/5z9l PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5z9l ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/GYRB_ECOLI GYRB_ECOLI]] DNA gyrase negatively supercoils closed circular double-stranded DNA in an ATP-dependent manner and also catalyzes the interconversion of other topological isomers of double-stranded DNA rings, including catenanes and knotted rings.<ref>PMID:12051843</ref> <ref>PMID:18642932</ref> <ref>PMID:20675723</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Discovery of new drug binding sites on well-established targets is of great interest as it facilitates the design of new mechanistic inhibitors to overcome the acquired drug resistance. Small chemical fragments can easily enter and bind to the cavities on the protein surface. Thus, they can be used to probe new druggable pockets in proteins. DNA gyrase plays indispensable roles in DNA replication, and both its GyrA and GyrB subunits are clinically validated antibacterial targets. New mechanistic GyrB inhibitors are urgently desired since the withdrawal of novobiocin from the market by the FDA due to its reduced efficiency and other reasons. Here, a fragment library was screened against the E. coli GyrB ATPase domain by combining affinity- and bioactivity-based approaches. The following X-ray crystallographic efforts were made to determine the cocrystal structures of GyrB with ten fragment hits, and three different binding modes were disclosed. Fortunately, a hydrophobic pocket which is previously unknown was identified by two fragments. Fragments that bind to this pocket were shown to inhibit the ATPase activity as well as the DNA topological transition activity of DNA gyrase in vitro. A set of fragment analogs were screened to explore the binding capacity of this pocket and identify the better starting fragments for lead development. Phylogenetic analysis revealed that this pocket is conserved in most Gram-negative and also many Gram-positive human pathogenic bacteria, implying a broad-spectrum antibacterial potential and a lower risk of mutation. Thus, the novel druggable pocket and the starting fragments provide a novel basis for designing new GyrB-targeting therapeutics.

-	~~Authors: Huang~~, X., ~~Zhou~~, H.	+	Identification of an auxiliary druggable pocket in the DNA gyrase ATPase domain using fragment probes.,Huang X, Guo J, Liu Q, Gu Q, Xu J, Zhou H Medchemcomm. 2018 Jul 4;9(10):1619-1629. doi: 10.1039/c8md00148k. eCollection, 2018 Oct 1. PMID:30429968<ref>PMID:30429968</ref>

-	~~Description: Bacterial GyrB ATPase domain in complex with~~ a ~~chemical fragment~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[Category: Unreleased Structures]]~~	+	</div>
-	~~[[Category~~: ~~Zhou, H]]~~	+	<div class="pdbe-citations 5z9l" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
	[[Category: Huang, X]]		[[Category: Huang, X]]
		+	[[Category: Zhou, H]]
		+	[[Category: Antibacterial]]
		+	[[Category: Dna topoisomerase]]
		+	[[Category: Drug target]]
		+	[[Category: Fragment-base lead discovery]]
		+	[[Category: Isomerase]]

OCA: Protected "5z9l" [edit=sysop:move=sysop]

OCA — Thu, 15 Feb 2018 05:09:39 GMT

Protected "5z9l" [edit=sysop:move=sysop]

←Older revision

Revision as of 05:09, 15 February 2018

OCA: New page: '''Unreleased structure''' The entry 5z9l is ON HOLD until Paper Publication Authors: Huang, X., Zhou, H. Description: Bacterial GyrB ATPase domain in complex with a chemical fragment ...

OCA — Thu, 15 Feb 2018 05:09:38 GMT

New page: '''Unreleased structure''' The entry 5z9l is ON HOLD until Paper Publication Authors: Huang, X., Zhou, H. Description: Bacterial GyrB ATPase domain in complex with a chemical fragment ...

New page

'''Unreleased structure'''

The entry 5z9l is ON HOLD until Paper Publication

Authors: Huang, X., Zhou, H.

Description: Bacterial GyrB ATPase domain in complex with a chemical fragment
[[Category: Unreleased Structures]]
[[Category: Zhou, H]]
[[Category: Huang, X]]