rdf:type |
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lifeskim:mentions |
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pubmed:issue |
5
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pubmed:dateCreated |
2009-2-4
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pubmed:databankReference |
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pubmed:abstractText |
Staphylococcus aureus synthesizes polyglycerol-phosphate lipoteichoic acid (LTA) from phosphatidylglycerol. LtaS, a predicted membrane protein with 5 N-terminal transmembrane helices followed by a large extracellular part (eLtaS), is required for staphylococcal growth and LTA synthesis. Here, we report the first crystal structure of the eLtaS domain at 1.2-A resolution and show that it assumes a sulfatase-like fold with an alpha/beta core and a C-terminal part composed of 4 anti-parallel beta-strands and a long alpha-helix. Overlaying eLtaS with sulfatase structures identified active site residues, which were confirmed by alanine substitution mutagenesis and in vivo enzyme function assays. The cocrystal structure with glycerol-phosphate and the coordination of a Mn(2+) cation allowed us to propose a reaction mechanism, whereby the active site threonine of LtaS functions as nucleophile for phosphatidylglycerol hydrolysis and formation of a covalent threonine-glycerolphosphate intermediate. These results will aid in the development of LtaS-specific inhibitors for S. aureus and many other Gram-positive pathogens.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/19168632-10658653,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19168632-10747010,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19168632-10924740,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19168632-11320452,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19168632-11435113,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/19168632-12142482,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19168632-15299374,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19168632-15572765,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19168632-15909267,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/19168632-16470658,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19168632-17209021,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/19168632-18156677,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19168632-18227251,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/19168632-9709046
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
1091-6490
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:day |
3
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pubmed:volume |
106
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1584-9
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
pubmed-meshheading:19168632-Bacterial Proteins,
pubmed-meshheading:19168632-Catalytic Domain,
pubmed-meshheading:19168632-Hydrolysis,
pubmed-meshheading:19168632-Lipopolysaccharides,
pubmed-meshheading:19168632-Manganese,
pubmed-meshheading:19168632-Models, Molecular,
pubmed-meshheading:19168632-Mutagenesis, Site-Directed,
pubmed-meshheading:19168632-Protein Conformation,
pubmed-meshheading:19168632-Staphylococcus aureus,
pubmed-meshheading:19168632-Teichoic Acids
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pubmed:year |
2009
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pubmed:articleTitle |
Structure-based mechanism of lipoteichoic acid synthesis by Staphylococcus aureus LtaS.
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pubmed:affiliation |
Division of Molecular Biosciences, Department of Microbiology, Imperial College London, South Kensington Campus, London SW7 2AZ, United Kingdom.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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