Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2009-2-4
pubmed:databankReference
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.
pubmed:grant
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, http://linkedlifedata.com/resource/pubmed/commentcorrection/19168632-11681202, 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, http://linkedlifedata.com/resource/pubmed/commentcorrection/19168632-16121336, http://linkedlifedata.com/resource/pubmed/commentcorrection/19168632-16470658, http://linkedlifedata.com/resource/pubmed/commentcorrection/19168632-17209021, http://linkedlifedata.com/resource/pubmed/commentcorrection/19168632-17483484, http://linkedlifedata.com/resource/pubmed/commentcorrection/19168632-17558559, http://linkedlifedata.com/resource/pubmed/commentcorrection/19168632-18156677, http://linkedlifedata.com/resource/pubmed/commentcorrection/19168632-18227251, http://linkedlifedata.com/resource/pubmed/commentcorrection/19168632-18257700, http://linkedlifedata.com/resource/pubmed/commentcorrection/19168632-18614239, http://linkedlifedata.com/resource/pubmed/commentcorrection/19168632-2668036, http://linkedlifedata.com/resource/pubmed/commentcorrection/19168632-3289326, http://linkedlifedata.com/resource/pubmed/commentcorrection/19168632-6304004, http://linkedlifedata.com/resource/pubmed/commentcorrection/19168632-638158, http://linkedlifedata.com/resource/pubmed/commentcorrection/19168632-7240097, http://linkedlifedata.com/resource/pubmed/commentcorrection/19168632-7494036, http://linkedlifedata.com/resource/pubmed/commentcorrection/19168632-7935161, http://linkedlifedata.com/resource/pubmed/commentcorrection/19168632-8824617, http://linkedlifedata.com/resource/pubmed/commentcorrection/19168632-9249217, http://linkedlifedata.com/resource/pubmed/commentcorrection/19168632-9709046
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1091-6490
pubmed:author
pubmed:issnType
Electronic
pubmed:day
3
pubmed:volume
106
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1584-9
pubmed:dateRevised
2009-11-18
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Structure-based mechanism of lipoteichoic acid synthesis by Staphylococcus aureus LtaS.
pubmed:affiliation
Division of Molecular Biosciences, Department of Microbiology, Imperial College London, South Kensington Campus, London SW7 2AZ, United Kingdom.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural