8ogs - Revision history

OCA at 06:16, 14 May 2025

2025-05-14T06:16:32Z

← Older revision		Revision as of 06:16, 14 May 2025
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	<table><tr><td colspan='2'>[[8ogs]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Bacillus_subtilis_subsp._subtilis_str._168 Bacillus subtilis subsp. subtilis str. 168]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8OGS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8OGS FirstGlance]. <br>		<table><tr><td colspan='2'>[[8ogs]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Bacillus_subtilis_subsp._subtilis_str._168 Bacillus subtilis subsp. subtilis str. 168]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8OGS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8OGS FirstGlance]. <br>
	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution\|Resolution]] 1.25Å</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]] 1.25Å</td></tr>
	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=T9S:ethyl+1,3-~~dihydro-2H-pyrrolo~~[3,4-c]pyridine-2-carboxylate'>T9S</scene></td></tr>		<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=T9S:ethyl+1,3-dihydropyrrolo[3,4-c]pyridine-2-carboxylate'>T9S</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=8ogs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8ogs OCA], [https://pdbe.org/8ogs PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8ogs RCSB], [https://www.ebi.ac.uk/pdbsum/8ogs PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8ogs 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=8ogs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8ogs OCA], [https://pdbe.org/8ogs PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8ogs RCSB], [https://www.ebi.ac.uk/pdbsum/8ogs PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8ogs ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
	[https://www.uniprot.org/uniprot/CDAA_BACSU CDAA_BACSU] One of 3 paralogous diadenylate cyclases (DAC) in this bacteria, catalyzing the condensation of 2 ATP molecules into cyclic di-AMP (c-di-AMP) (Probable). Upon expression in E.coli leads to c-di-AMP synthesis (PubMed:23192352). Probably the main producer of c-di-AMP for the cell; is probably implicated in control of ~~peptidogylcan~~ synthesis (PubMed:22211522, PubMed:23192352, PubMed:26240071). In B.subtilis c-di-AMP is a second messenger that mediates growth, DNA repair and cell wall homeostasis; it is toxic when present in excess (PubMed:26240071).<ref>PMID:23192352</ref> <ref>PMID:26240071</ref> <ref>PMID:22211522</ref>		[https://www.uniprot.org/uniprot/CDAA_BACSU CDAA_BACSU] One of 3 paralogous diadenylate cyclases (DAC) in this bacteria, catalyzing the condensation of 2 ATP molecules into cyclic di-AMP (c-di-AMP) (Probable). Upon expression in E.coli leads to c-di-AMP synthesis (PubMed:23192352). Probably the main producer of c-di-AMP for the cell; is probably implicated in control of peptidoglycan synthesis (PubMed:22211522, PubMed:23192352, PubMed:26240071). In B.subtilis c-di-AMP is a second messenger that mediates growth, DNA repair and cell wall homeostasis; it is toxic when present in excess (PubMed:26240071).<ref>PMID:23192352</ref> <ref>PMID:26240071</ref> <ref>PMID:22211522</ref>
			<div style="background-color:#fffaf0;">
			== Publication Abstract from PubMed ==
			Crystallographic fragment screening has become a pivotal technique in structure-based drug design, particularly for bacterial targets with a crucial role in infectious disease mechanisms. The enzyme CdaA, which synthesizes an essential second messenger cyclic di-AMP (c-di-AMP) in many pathogenic bacteria, has emerged as a promising candidate for the development of novel antibiotics. To identify crystals suitable for fragment screening, CdaA enzymes from Streptococcus pneumoniae, Bacillus subtilis and Enterococcus faecium were purified and crystallized. Crystals of B. subtilis CdaA, which diffracted to the highest resolution of 1.1 A, were used to perform the screening of 96 fragments, yielding data sets with resolutions spanning from 1.08 to 1.87 A. A total of 24 structural hits across eight different sites were identified. Four fragments bind to regions that are highly conserved among pathogenic bacteria, specifically the active site (three fragments) and the dimerization interface (one fragment). The coordinates of the three active-site fragments were used to perform an in silico drug-repurposing screen using the OpenEye suite and the DrugBank database. This screen identified tenofovir, an approved drug, that is predicted to interact with the ATP-binding region of CdaA. Its inhibitory potential against pathogenic E. faecium CdaA has been confirmed by ITC measurements. These findings not only demonstrate the feasibility of this approach for identifying lead compounds for the design of novel antibacterial agents, but also pave the way for further fragment-based lead-optimization efforts targeting CdaA.

			Crystallographic fragment screen of the c-di-AMP-synthesizing enzyme CdaA from Bacillus subtilis.,Garbers T, Neumann P, Wollenhaupt J, Dickmanns A, Weiss MS, Ficner R Acta Crystallogr F Struct Biol Commun. 2024 Sep 1;80(Pt 9):200-209. doi: , 10.1107/S2053230X24007039. Epub 2024 Aug 23. PMID:39177700<ref>PMID:39177700</ref>

			From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
			</div>
			<div class="pdbe-citations 8ogs" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>

OCA at 10:10, 27 March 2024

2024-03-27T10:10:18Z

← Older revision		Revision as of 10:10, 27 March 2024
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	~~'''Unreleased structure'''~~

	~~The entry~~ 8ogs is ~~ON HOLD until Paper Publication~~		==PanDDA analysis group deposition -- CdaA in complex with fragment F2X-Entry B08==
			<StructureSection load='8ogs' size='340' side='right'caption='[[8ogs]], [[Resolution\|resolution]] 1.25Å' scene=''>
	~~Authors~~: ~~Garbers~~, T.B., ~~Neumann~~, P., ~~Wollenhaupt~~, J.~~, Weiss, M~~.S., ~~Ficner, R~~.		== Structural highlights ==
			<table><tr><td colspan='2'>[[8ogs]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Bacillus_subtilis_subsp._subtilis_str._168 Bacillus subtilis subsp. subtilis str. 168]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8OGS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8OGS FirstGlance]. <br>
	~~Description~~: ~~PanDDA analysis group deposition~~ --~~CdaA~~ in ~~complex with fragment F2X~~-~~Entry B08~~		</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution\|Resolution]] 1.25Å</td></tr>
	[[Category: ~~Unreleased~~ Structures]]		<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=T9S:ethyl+1,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxylate'>T9S</scene></td></tr>
	[[Category: Ficner, R]]		<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=8ogs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8ogs OCA], [https://pdbe.org/8ogs PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8ogs RCSB], [https://www.ebi.ac.uk/pdbsum/8ogs PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8ogs ProSAT]</span></td></tr>
	[[Category: ~~Wollenhaupt, J~~]]		</table>
	[[Category: Neumann, P]]		== Function ==
	[[Category: ~~Garbers, T.B~~]]		[https://www.uniprot.org/uniprot/CDAA_BACSU CDAA_BACSU] One of 3 paralogous diadenylate cyclases (DAC) in this bacteria, catalyzing the condensation of 2 ATP molecules into cyclic di-AMP (c-di-AMP) (Probable). Upon expression in E.coli leads to c-di-AMP synthesis (PubMed:23192352). Probably the main producer of c-di-AMP for the cell; is probably implicated in control of peptidogylcan synthesis (PubMed:22211522, PubMed:23192352, PubMed:26240071). In B.subtilis c-di-AMP is a second messenger that mediates growth, DNA repair and cell wall homeostasis; it is toxic when present in excess (PubMed:26240071).<ref>PMID:23192352</ref> <ref>PMID:26240071</ref> <ref>PMID:22211522</ref>
	[[Category: ~~Weiss, M.S~~]]		== References ==
			<references/>
			__TOC__
			</StructureSection>
			[[Category: Bacillus subtilis subsp. subtilis str. 168]]
			[[Category: Large Structures]]
			[[Category: Ficner R]]
			[[Category: Garbers TB]]
			[[Category: Neumann P]]
			[[Category: Weiss MS]]
			[[Category: Wollenhaupt J]]

OCA at 08:06, 19 April 2023

2023-04-19T08:06:11Z

← Older revision		Revision as of 08:06, 19 April 2023
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	'''Unreleased structure'''		'''Unreleased structure'''

	The entry 8ogs is ON HOLD		The entry 8ogs is ON HOLD until Paper Publication

	Authors: Garbers, T.B., Neumann, P., Wollenhaupt, J., Weiss, M.S., Ficner, R.		Authors: Garbers, T.B., Neumann, P., Wollenhaupt, J., Weiss, M.S., Ficner, R.

OCA: Protected "8ogs" [edit=sysop:move=sysop]

2023-03-29T05:05:46Z

Protected "8ogs" [edit=sysop:move=sysop]

← Older revision	Revision as of 05:05, 29 March 2023
(No difference)

OCA: New page: '''Unreleased structure''' The entry 8ogs is ON HOLD Authors: Garbers, T.B., Neumann, P., Wollenhaupt, J., Weiss, M.S., Ficner, R. Description: PanDDA analysis group deposition --CdaA ...

2023-03-29T05:05:45Z

New page: '''Unreleased structure''' The entry 8ogs is ON HOLD Authors: Garbers, T.B., Neumann, P., Wollenhaupt, J., Weiss, M.S., Ficner, R. Description: PanDDA analysis group deposition --CdaA ...

New page

'''Unreleased structure'''

The entry 8ogs is ON HOLD

Authors: Garbers, T.B., Neumann, P., Wollenhaupt, J., Weiss, M.S., Ficner, R.

Description: PanDDA analysis group deposition --CdaA in complex with fragment F2X-Entry B08
[[Category: Unreleased Structures]]
[[Category: Ficner, R]]
[[Category: Wollenhaupt, J]]
[[Category: Neumann, P]]
[[Category: Garbers, T.B]]
[[Category: Weiss, M.S]]