6ny0 - Revision history

OCA at 07:01, 11 October 2023

OCA — Wed, 11 Oct 2023 07:01:33 GMT

←Older revision		Revision as of 07:01, 11 October 2023
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	<StructureSection load='6ny0' size='340' side='right'caption='[[6ny0]], [[Resolution\|resolution]] 1.40Å' scene=''>		<StructureSection load='6ny0' size='340' side='right'caption='[[6ny0]], [[Resolution\|resolution]] 1.40Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6ny0]] is a 1 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~"bacillus_coli"_migula_1895 "bacillus~~ coli~~" migula 1895~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6NY0 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6NY0 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6ny0]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6NY0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6NY0 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=LBA:2-(4-{3-[4-(6-carboxy-1H-benzimidazol-2-yl)phenoxy]-2-hydroxypropoxy}phenyl)-1H-benzimidazole-5-carboxylic+acid'>LBA</scene>, <scene name='pdbligand=MRD:(4R)-2-METHYLPENTANE-2,4-DIOL'>MRD</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]] 1.4Å</td></tr>
-	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Dihydrofolate_reductase Dihydrofolate reductase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.5.1.3 1.5.1.3] </span></td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=LBA:2-(4-{3-[4-(6-carboxy-1H-benzimidazol-2-yl)phenoxy]-2-hydroxypropoxy}phenyl)-1H-benzimidazole-5-carboxylic+acid'>LBA</scene>, <scene name='pdbligand=MRD:(4R)-2-METHYLPENTANE-2,4-DIOL'>MRD</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~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6ny0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ny0 OCA], [~~http~~://pdbe.org/6ny0 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6ny0 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6ny0 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6ny0 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=6ny0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ny0 OCA], [https://pdbe.org/6ny0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6ny0 RCSB], [https://www.ebi.ac.uk/pdbsum/6ny0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6ny0 ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/DYR21_ECOLX DYR21_ECOLX]] Key enzyme in folate metabolism. Catalyzes an essential reaction for de novo glycine and purine synthesis, and for DNA precursor synthesis.	+	[https://www.uniprot.org/uniprot/DYR21_ECOLX DYR21_ECOLX] Key enzyme in folate metabolism. Catalyzes an essential reaction for de novo glycine and purine synthesis, and for DNA precursor synthesis.
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 26:		Line 26:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Bacillus~~ coli ~~migula 1895]]~~	+	[[Category: Escherichia coli]]
-	~~[[Category: Dihydrofolate reductase~~]]	+
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Berghuis~~, A M~~]]	+	[[Category: Berghuis AM]]
-	[[Category: Yachnin~~, B J]]~~	+	[[Category: Yachnin BJ]]
-	~~[[Category: Antibiotic]]~~	+
-	~~[[Category: Antibiotic resistance]]~~	+
-	~~[[Category: Oxidoreductase]]~~	+
-	~~[[Category: R67 dhfr]]~~	+
-	~~[[Category: Selective inhibitor]]~~	+
-	~~[[Category: Sh3-like barrel~~]]	+

OCA at 09:23, 8 January 2020

OCA — Wed, 08 Jan 2020 09:23:48 GMT

←Older revision		Revision as of 09:23, 8 January 2020
Line 10:		Line 10:
	== Function ==		== Function ==
	[[http://www.uniprot.org/uniprot/DYR21_ECOLX DYR21_ECOLX]] Key enzyme in folate metabolism. Catalyzes an essential reaction for de novo glycine and purine synthesis, and for DNA precursor synthesis.		[[http://www.uniprot.org/uniprot/DYR21_ECOLX DYR21_ECOLX]] Key enzyme in folate metabolism. Catalyzes an essential reaction for de novo glycine and purine synthesis, and for DNA precursor synthesis.
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The worldwide use of the broad-spectrum antimicrobial trimethoprim (TMP) has induced the rise of TMP-resistant microorganisms. In addition to resistance-causing mutations of the microbial chromosomal dihydrofolate reductase (Dfr), the evolutionarily and structurally unrelated type II Dfrs (DfrBs) have been identified in TMP-resistant microorganisms. DfrBs are intrinsically TMP-resistant and allow bacterial proliferation when the microbial chromosomal Dfr is TMP-inhibited, making these enzymes important targets for inhibitor development. Furthermore, DfrBs occur in multiresistance plasmids, potentially accelerating their dissemination. We previously reported symmetrical bisbenzimidazoles that are the first selective inhibitors of the only well-characterized DfrB, DfrB1. Here, their diversification provides a new series of inhibitors (K i = 1.7-12.0 muM). Our results reveal two prominent features: terminal carboxylates and inhibitor length allow the establishment of essential interactions with DfrB1. Two crystal structures demonstrate the simultaneous binding of two inhibitor molecules in the symmetrical active site. Observations of those dimeric inhibitors inspired the design of monomeric analogues, binding in a single copy yet offering similar inhibition potency (K i = 1.1 and 7.4 muM). Inhibition of a second member of the DfrB family, DfrB4, suggests the generality of these inhibitors. These results provide key insights into inhibition of the highly TMP-resistant DfrBs, opening avenues to downstream development of antibiotics for combatting this emergent source of resistance.
		+
		+	Structure-Based Design of Dimeric Bisbenzimidazole Inhibitors to an Emergent Trimethoprim-Resistant Type II Dihydrofolate Reductase Guides the Design of Monomeric Analogues.,Toulouse JL, Yachnin BJ, Ruediger EH, Deon D, Gagnon M, Saint-Jacques K, Ebert MCCJC, Forge D, Bastien D, Colin DY, Vanden Eynde JJ, Marinier A, Berghuis AM, Pelletier JN ACS Omega. 2019 Jun 10;4(6):10056-10069. doi: 10.1021/acsomega.9b00640., eCollection 2019 Jun 30. PMID:31460098<ref>PMID:31460098</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 6ny0" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
	*[[Dihydrofolate reductase 3D structures\|Dihydrofolate reductase 3D structures]]		*[[Dihydrofolate reductase 3D structures\|Dihydrofolate reductase 3D structures]]
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>

OCA at 06:55, 3 July 2019

OCA — Wed, 03 Jul 2019 06:55:27 GMT

←Older revision		Revision as of 06:55, 3 July 2019
Line 3:		Line 3:
	<StructureSection load='6ny0' size='340' side='right'caption='[[6ny0]], [[Resolution\|resolution]] 1.40Å' scene=''>		<StructureSection load='6ny0' size='340' side='right'caption='[[6ny0]], [[Resolution\|resolution]] 1.40Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6ny0]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6NY0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6NY0 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6ny0]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_coli"_migula_1895 "bacillus coli" migula 1895]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6NY0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6NY0 FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=LBA:2-(4-{3-[4-(6-carboxy-1H-benzimidazol-2-yl)phenoxy]-2-hydroxypropoxy}phenyl)-1H-benzimidazole-5-carboxylic+acid'>LBA</scene>, <scene name='pdbligand=MRD:(4R)-2-METHYLPENTANE-2,4-DIOL'>MRD</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"><scene name='pdbligand=LBA:2-(4-{3-[4-(6-carboxy-1H-benzimidazol-2-yl)phenoxy]-2-hydroxypropoxy}phenyl)-1H-benzimidazole-5-carboxylic+acid'>LBA</scene>, <scene name='pdbligand=MRD:(4R)-2-METHYLPENTANE-2,4-DIOL'>MRD</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/Dihydrofolate_reductase Dihydrofolate reductase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.5.1.3 1.5.1.3] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Dihydrofolate_reductase Dihydrofolate reductase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.5.1.3 1.5.1.3] </span></td></tr>
Line 10:		Line 10:
	== Function ==		== Function ==
	[[http://www.uniprot.org/uniprot/DYR21_ECOLX DYR21_ECOLX]] Key enzyme in folate metabolism. Catalyzes an essential reaction for de novo glycine and purine synthesis, and for DNA precursor synthesis.		[[http://www.uniprot.org/uniprot/DYR21_ECOLX DYR21_ECOLX]] Key enzyme in folate metabolism. Catalyzes an essential reaction for de novo glycine and purine synthesis, and for DNA precursor synthesis.
		+
		+	==See Also==
		+	*[[Dihydrofolate reductase 3D structures\|Dihydrofolate reductase 3D structures]]
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Bacillus coli migula 1895]]
	[[Category: Dihydrofolate reductase]]		[[Category: Dihydrofolate reductase]]
	[[Category: Large Structures]]		[[Category: Large Structures]]

OCA at 06:15, 29 May 2019

OCA — Wed, 29 May 2019 06:15:20 GMT

←Older revision		Revision as of 06:15, 29 May 2019
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry 6ny0 is ON HOLD until Paper Publication~~	+	==Crystal structure of trimethoprim-resistant type II dihydrofolate reductase in complex with a bisbenzimidazole inhibitor==
-		+	<StructureSection load='6ny0' size='340' side='right'caption='[[6ny0]], [[Resolution\|resolution]] 1.40Å' scene=''>
-	~~Authors: Yachnin, B.J., Berghuis, A.M.~~	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[6ny0]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6NY0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6NY0 FirstGlance]. <br>
-	~~Description:~~ Crystal structure of trimethoprim-resistant type II dihydrofolate reductase in complex with a bisbenzimidazole inhibitor	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=LBA:2-(4-{3-[4-(6-carboxy-1H-benzimidazol-2-yl)phenoxy]-2-hydroxypropoxy}phenyl)-1H-benzimidazole-5-carboxylic+acid'>LBA</scene>, <scene name='pdbligand=MRD:(4R)-2-METHYLPENTANE-2,4-DIOL'>MRD</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Dihydrofolate_reductase Dihydrofolate reductase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.5.1.3 1.5.1.3] </span></td></tr>
-	[[Category: Yachnin, B.J]]	+	<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=6ny0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ny0 OCA], [http://pdbe.org/6ny0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ny0 RCSB], [http://www.ebi.ac.uk/pdbsum/6ny0 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ny0 ProSAT]</span></td></tr>
-	[[Category: ~~Berghuis, A.M~~]]	+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/DYR21_ECOLX DYR21_ECOLX]] Key enzyme in folate metabolism. Catalyzes an essential reaction for de novo glycine and purine synthesis, and for DNA precursor synthesis.
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Dihydrofolate reductase]]
		+	[[Category: Large Structures]]
		+	[[Category: Berghuis, A M]]
		+	[[Category: Yachnin, B J]]
		+	[[Category: Antibiotic]]
		+	[[Category: Antibiotic resistance]]
		+	[[Category: Oxidoreductase]]
		+	[[Category: R67 dhfr]]
		+	[[Category: Selective inhibitor]]
		+	[[Category: Sh3-like barrel]]

OCA at 10:08, 13 March 2019

OCA — Wed, 13 Mar 2019 10:08:34 GMT

←Older revision		Revision as of 10:08, 13 March 2019
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 6ny0 is ON HOLD	+	The entry 6ny0 is ON HOLD until Paper Publication

	Authors: Yachnin, B.J., Berghuis, A.M.		Authors: Yachnin, B.J., Berghuis, A.M.

OCA: Protected "6ny0" [edit=sysop:move=sysop]

OCA — Thu, 21 Feb 2019 05:12:44 GMT

Protected "6ny0" [edit=sysop:move=sysop]

←Older revision

Revision as of 05:12, 21 February 2019

OCA: New page: '''Unreleased structure''' The entry 6ny0 is ON HOLD Authors: Yachnin, B.J., Berghuis, A.M. Description: Crystal structure of trimethoprim-resistant type II dihydrofolate reductase in ...

OCA — Thu, 21 Feb 2019 05:12:42 GMT

New page: '''Unreleased structure''' The entry 6ny0 is ON HOLD Authors: Yachnin, B.J., Berghuis, A.M. Description: Crystal structure of trimethoprim-resistant type II dihydrofolate reductase in ...

New page

'''Unreleased structure'''

The entry 6ny0 is ON HOLD

Authors: Yachnin, B.J., Berghuis, A.M.

Description: Crystal structure of trimethoprim-resistant type II dihydrofolate reductase in complex with a bisbenzimidazole inhibitor
[[Category: Unreleased Structures]]
[[Category: Yachnin, B.J]]
[[Category: Berghuis, A.M]]