Structural highlights
Function[LTAS_STAAW] Catalyzes the polymerization of lipoteichoic acid (LTA) polyglycerol phosphate, a reaction that presumably uses phosphatidylglycerol (PG) as substrate. Is required for staphylococcal growth and cell division process (By similarity). Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedStaphylococcus 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. Structure-based mechanism of lipoteichoic acid synthesis by Staphylococcus aureus LtaS.,Lu D, Wormann ME, Zhang X, Schneewind O, Grundling A, Freemont PS Proc Natl Acad Sci U S A. 2009 Jan 23. PMID:19168632[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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