2W5Q

Structure-based mechanism of lipoteichoic acid synthesis by Staphylococcus aureus LtaS.

Summary for 2W5Q

• Entry DOI: 10.2210/pdb2w5q/pdb
• Related: 2W5R 2W5S 2W5T
• Descriptor: PROCESSED GLYCEROL PHOSPHATE LIPOTEICHOIC ACID SYNTHASE, MANGANESE (II) ION, 1,2-ETHANEDIOL, ... (4 entities in total)
• Functional Keywords: transmembrane, cell wall biogenesis/degradation, ltas, membrane, secreted, transferase, cell membrane
• Biological source: STAPHYLOCOCCUS AUREUS
• Cellular location: Cell membrane; Multi-pass membrane protein (Potential). Processed glycerol phosphate lipoteichoic acid synthase: Secreted (By similarity): Q7A1I3
• Total number of polymer chains: 1
• Total formula weight: 48987.69

Authors

Lu, D.,Wormann, M.E.,Zhang, X.,Scheewind, O.,Grundling, A.,Freemont, P.S. (deposition date: 2008-12-11, release date: 2009-02-03, Last modification date: 2024-05-08)

Primary citation

Lu, D.,Wormann, M.E.,Zhang, X.,Schneewind, O.,Grundling, A.,Freemont, P.S.
Structure-Based Mechanism of Lipoteichoic Acid Synthesis by Staphylococcus Aureus Ltas.
Proc.Natl.Acad.Sci.USA, 106:1584-, 2009

PubMed Abstract: 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: 19168632
DOI: 10.1073/PNAS.0809020106

Experimental method

X-RAY DIFFRACTION (1.2 Å)