7rfl - Revision history

OCA at 16:30, 18 October 2023

OCA — Wed, 18 Oct 2023 16:30:43 GMT

←Older revision		Revision as of 16:30, 18 October 2023
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	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[7rfl]] is a 9 chain structure with sequence from [https://en.wikipedia.org/wiki/Clostridioides_difficile Clostridioides difficile] and [https://en.wikipedia.org/wiki/Clostridioides_difficile_630 Clostridioides difficile 630]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7RFL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7RFL FirstGlance]. <br>		<table><tr><td colspan='2'>[[7rfl]] is a 9 chain structure with sequence from [https://en.wikipedia.org/wiki/Clostridioides_difficile Clostridioides difficile] and [https://en.wikipedia.org/wiki/Clostridioides_difficile_630 Clostridioides difficile 630]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7RFL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7RFL FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AW2:5-BROMO-7-{5-[(3-{[(4-TERT-BUTYLPHENYL)CARBAMOYL]AMINO}PROPYL)(PROPAN-2-YL)AMINO]-5-DEOXY-BETA-D-RIBOFURANOSYL}-7H-PYRROLO[2,3-D]PYRIMIDIN-4-AMINE'>AW2</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</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]] 2.38Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AW2:5-BROMO-7-{5-[(3-{[(4-TERT-BUTYLPHENYL)CARBAMOYL]AMINO}PROPYL)(PROPAN-2-YL)AMINO]-5-DEOXY-BETA-D-RIBOFURANOSYL}-7H-PYRROLO[2,3-D]PYRIMIDIN-4-AMINE'>AW2</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</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=7rfl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7rfl OCA], [https://pdbe.org/7rfl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7rfl RCSB], [https://www.ebi.ac.uk/pdbsum/7rfl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7rfl 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=7rfl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7rfl OCA], [https://pdbe.org/7rfl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7rfl RCSB], [https://www.ebi.ac.uk/pdbsum/7rfl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7rfl ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[https://www.uniprot.org/uniprot/Q183J3_CLOD6 Q183J3_CLOD6]]	+	[https://www.uniprot.org/uniprot/Q183J3_CLOD6 Q183J3_CLOD6]
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 18:		Line 19:
	</div>		</div>
	<div class="pdbe-citations 7rfl" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 7rfl" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[DNA methyltransferase 3D structures\|DNA methyltransferase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 06:27, 28 September 2022

OCA — Wed, 28 Sep 2022 06:27:53 GMT

←Older revision		Revision as of 06:27, 28 September 2022
Line 1:		Line 1:

-	====	+	==CamA Adenine Methyltransferase Complexed to Cognate Substrate DNA and Inhibitor SGC0946==
-	<StructureSection load='7rfl' size='340' side='right'caption='[[7rfl]]' scene=''>	+	<StructureSection load='7rfl' size='340' side='right'caption='[[7rfl]], [[Resolution\|resolution]] 2.38Å' 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= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7rfl]] is a 9 chain structure with sequence from [https://en.wikipedia.org/wiki/Clostridioides_difficile Clostridioides difficile] and [https://en.wikipedia.org/wiki/Clostridioides_difficile_630 Clostridioides difficile 630]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7RFL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7RFL 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=7rfl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7rfl OCA], [https://pdbe.org/7rfl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7rfl RCSB], [https://www.ebi.ac.uk/pdbsum/7rfl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7rfl 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=AW2:5-BROMO-7-{5-[(3-{[(4-TERT-BUTYLPHENYL)CARBAMOYL]AMINO}PROPYL)(PROPAN-2-YL)AMINO]-5-DEOXY-BETA-D-RIBOFURANOSYL}-7H-PYRROLO[2,3-D]PYRIMIDIN-4-AMINE'>AW2</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</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=7rfl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7rfl OCA], [https://pdbe.org/7rfl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7rfl RCSB], [https://www.ebi.ac.uk/pdbsum/7rfl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7rfl ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[[https://www.uniprot.org/uniprot/Q183J3_CLOD6 Q183J3_CLOD6]]
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Epigenetically targeted therapeutic development, particularly for SAM-dependent methylations of DNA, mRNA and histones has been proceeding rapidly for cancer treatments over the past few years. However, this approach has barely begun to be exploited for developing new antibiotics, despite an overwhelming global need to counter antimicrobial resistance. Here, we explore whether SAM analogues, some of which are in (pre)clinical studies as inhibitors of human epigenetic enzymes, can also inhibit Clostridioides difficile-specific DNA adenine methyltransferase (CamA), a sporulation regulator present in all C. difficile genomes sequenced to date, but found in almost no other bacteria. We found that SGC0946 (an inhibitor of DOT1L), JNJ-64619178 (an inhibitor of PRMT5) and SGC8158 (an inhibitor of PRMT7) inhibit CamA enzymatic activity in vitro at low micromolar concentrations. Structural investigation of the ternary complexes of CamA-DNA in the presence of SGC0946 or SGC8158 revealed conformational rearrangements of the N-terminal arm, with no apparent disturbance of the active site. This N-terminal arm and its modulation of exchanges between SAM (the methyl donor) and SAH (the reaction product) during catalysis of methyl transfer are, to date, unique to CamA. Our work presents a substantial first step in generating potent and selective inhibitors of CamA that would serve in the near term as chemical probes to investigate the cellular mechanism(s) of CamA in controlling spore formation and colonization, and eventually as therapeutic antivirulence agents useful in treating C. difficile infection.
		+
		+	Repurposing epigenetic inhibitors to target the Clostridioides difficile-specific DNA adenine methyltransferase and sporulation regulator CamA.,Zhou J, Horton JR, Yu D, Ren R, Blumenthal RM, Zhang X, Cheng X Epigenetics. 2022 Sep;17(9):970-981. doi: 10.1080/15592294.2021.1976910. Epub, 2021 Sep 15. PMID:34523387<ref>PMID:34523387</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7rfl" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Clostridioides difficile]]
		+	[[Category: Clostridioides difficile 630]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: ~~Z-disk~~]]	+	[[Category: Cheng X]]
		+	[[Category: Horton JR]]
		+	[[Category: Zhou J]]

OCA at 09:30, 15 September 2021

OCA — Wed, 15 Sep 2021 09:30:32 GMT

←Older revision		Revision as of 09:30, 15 September 2021
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-	'''Unreleased structure'''

-	~~The entry~~ 7rfl ~~is ON HOLD~~	+	====
-		+	<StructureSection load='7rfl' size='340' side='right'caption='[[7rfl]]' scene=''>
-	~~Authors~~:	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br>
-	~~Description~~:	+	</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=7rfl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7rfl OCA], [https://pdbe.org/7rfl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7rfl RCSB], [https://www.ebi.ac.uk/pdbsum/7rfl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7rfl ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	</table>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Z-disk]]

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

OCA — Wed, 21 Jul 2021 08:03:31 GMT

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

←Older revision

Revision as of 08:03, 21 July 2021

OCA: New page: '''Unreleased structure''' The entry 7rfl is ON HOLD Authors: Description: Category: Unreleased Structures

OCA — Wed, 21 Jul 2021 08:03:31 GMT

New page: '''Unreleased structure''' The entry 7rfl is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 7rfl is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]