OCA at 09:30, 30 January 2019

OCA — Wed, 30 Jan 2019 09:30:21 GMT

←Older revision		Revision as of 09:30, 30 January 2019
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-	'''Unreleased structure'''

-	~~The entry~~ 6gyx is ~~ON HOLD until Paper~~ Publication	+	==Crystal structure of DacA from Staphylococcus aureus in complex with ApCpp==
		+	<StructureSection load='6gyx' size='340' side='right' caption='[[6gyx]], [[Resolution\|resolution]] 2.60Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[6gyx]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/"micrococcus_aureus"_(rosenbach_1884)_zopf_1885 "micrococcus aureus" (rosenbach 1884) zopf 1885]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6GYX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6GYX FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=APC:DIPHOSPHOMETHYLPHOSPHONIC+ACID+ADENOSYL+ESTER'>APC</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">dacA, C7J94_12115 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1280 "Micrococcus aureus" (Rosenbach 1884) Zopf 1885])</td></tr>
		+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Diadenylate_cyclase Diadenylate cyclase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.85 2.7.7.85] </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=6gyx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6gyx OCA], [http://pdbe.org/6gyx PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6gyx RCSB], [http://www.ebi.ac.uk/pdbsum/6gyx PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6gyx ProSAT]</span></td></tr>
		+	</table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	c-di-AMP is an important second messenger molecule that plays a pivotal role in regulating fundamental cellular processes, including osmotic and cell wall homeostasis in many Gram-positive organisms. In the opportunistic human pathogen Staphylococcus aureus, c-di-AMP is produced by the membrane-anchored DacA enzyme. Inactivation of this enzyme leads to a growth arrest under standard laboratory growth conditions and a re-sensitization of methicillin-resistant S. aureus (MRSA) strains to ss-lactam antibiotics. The gene coding for DacA is part of the conserved three-gene dacA/ybbR/glmM operon that also encodes the proposed DacA regulator YbbR and the essential phosphoglucosamine mutase GlmM, which is required for the production of glucosamine-1-phosphate, an early intermediate of peptidoglycan synthesis. These three proteins are thought to form a complex in vivo and, in this manner, help to fine-tune the cellular c-di-AMP levels. To further characterize this important regulatory complex, we conducted a comprehensive structural and functional analysis of the S. aureus DacA and GlmM enzymes by determining the structures of the S. aureus GlmM enzyme and the catalytic domain of DacA. Both proteins were found to be dimers in solution as well as in the crystal structures. Further site-directed mutagenesis, structural and enzymatic studies showed that multiple DacA dimers need to interact for enzymatic activity. We also show that DacA and GlmM form a stable complex in vitro and that S. aureus GlmM, but not Escherichia coli or Pseudomonas aeruginosa GlmM, acts as a strong inhibitor of DacA function without the requirement of any additional cellular factor. Based on Small Angle X-ray Scattering (SAXS) data, a model of the complex revealed that GlmM likely inhibits DacA by masking the active site of the cyclase and preventing higher oligomer formation. Together these results provide an important mechanistic insight into how c-di-AMP production can be regulated in the cell.

-	~~Authors: Tosi~~, T., ~~Freemont~~, P~~.S.~~, Grundling, A.	+	Inhibition of the Staphylococcus aureus c-di-AMP cyclase DacA by direct interaction with the phosphoglucosamine mutase GlmM.,Tosi T, Hoshiga F, Millership C, Singh R, Eldrid C, Patin D, Mengin-Lecreulx D, Thalassinos K, Freemont P, Grundling A PLoS Pathog. 2019 Jan 22;15(1):e1007537. doi: 10.1371/journal.ppat.1007537. PMID:30668586<ref>PMID:30668586</ref>

-	~~Description: Crystal structure~~ of ~~DacA from Staphylococcus aureus in complex with ApCpp~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased Structures~~]]	+	</div>
-	[[Category: ~~Tosi~~, T]]	+	<div class="pdbe-citations 6gyx" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Diadenylate cyclase]]
		+	[[Category: Freemont, P S]]
	[[Category: Grundling, A]]		[[Category: Grundling, A]]
-	[[Category: ~~Freemont~~, ~~P.S~~]]	+	[[Category: Tosi, T]]
		+	[[Category: Apcpp]]
		+	[[Category: C-di-amp]]
		+	[[Category: Transferase]]

OCA at 05:46, 18 July 2018

OCA — Wed, 18 Jul 2018 05:46:30 GMT

←Older revision		Revision as of 05:46, 18 July 2018
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	'''Unreleased structure'''		'''Unreleased structure'''

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

	Authors: Tosi, T., Freemont, P.S., Grundling, A.		Authors: Tosi, T., Freemont, P.S., Grundling, A.
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	Description: Crystal structure of DacA from Staphylococcus aureus in complex with ApCpp		Description: Crystal structure of DacA from Staphylococcus aureus in complex with ApCpp
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
-	[[Category: Freemont, P.S]]
	[[Category: Tosi, T]]		[[Category: Tosi, T]]
	[[Category: Grundling, A]]		[[Category: Grundling, A]]
		+	[[Category: Freemont, P.S]]

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

OCA — Wed, 11 Jul 2018 04:16:18 GMT

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

←Older revision

Revision as of 04:16, 11 July 2018

OCA: New page: '''Unreleased structure''' The entry 6gyx is ON HOLD Authors: Tosi, T., Freemont, P.S., Grundling, A. Description: Crystal structure of DacA from Staphylococcus aureus in complex with ...

OCA — Wed, 11 Jul 2018 04:16:17 GMT

New page: '''Unreleased structure''' The entry 6gyx is ON HOLD Authors: Tosi, T., Freemont, P.S., Grundling, A. Description: Crystal structure of DacA from Staphylococcus aureus in complex with ...

New page

'''Unreleased structure'''

The entry 6gyx is ON HOLD

Authors: Tosi, T., Freemont, P.S., Grundling, A.

Description: Crystal structure of DacA from Staphylococcus aureus in complex with ApCpp
[[Category: Unreleased Structures]]
[[Category: Freemont, P.S]]
[[Category: Tosi, T]]
[[Category: Grundling, A]]

6gyx - Revision history

OCA at 09:30, 30 January 2019

OCA at 05:46, 18 July 2018

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

OCA: New page: '''Unreleased structure''' The entry 6gyx is ON HOLD Authors: Tosi, T., Freemont, P.S., Grundling, A. Description: Crystal structure of DacA from Staphylococcus aureus in complex with ...