Structural and Mechanistic Insight into the Listeria monocytogenes Two-enzyme Lipoteichoic Acid Synthesis System
| Autor: | Ivan Campeotto, James M. MacDonald, Matthew G. Percy, Angelika Gründling, Paul S. Freemont, Andreas Förster |
|---|---|
| Přispěvatelé: | Medical Research Council (MRC), Commission of the European Communities |
| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Lipopolysaccharides
Models Molecular Protein Folding Plasma protein binding Crystallography X-Ray Biochemistry Protein Structure Secondary chemistry.chemical_compound Protein structure Cell Wall Catalytic Domain Transferase SYNTHASE Phylogeny chemistry.chemical_classification Teichoic acid 11 Medical And Health Sciences Lipid Recombinant Proteins LTA Synthesis Glycerophosphates Protein Structure and Folding Lipoteichoic acid Primase 03 Chemical Sciences Life Sciences & Biomedicine DATA QUALITY Protein Binding Biochemistry & Molecular Biology Protein Structure GRAM-POSITIVE BACTERIA Molecular Sequence Data Static Electricity Biology BACILLUS-SUBTILIS Bacterial Proteins Escherichia coli BIOSYNTHESIS Amino Acid Sequence Binding site Molecular Biology STAPHYLOCOCCUS-AUREUS Science & Technology Bacteria Cell Biology 06 Biological Sciences Listeria monocytogenes Protein Structure Tertiary MODEL Teichoic Acids Enzyme chemistry Enzyme Catalysis Mutagenesis Site-Directed |
| Zdroj: | The Journal of Biological Chemistry |
| Popis: | Background: Listeria monocytogenes lipoteichoic acid is synthesized by the LtaP/LtaS two-enzyme system. Results: Structural analysis reveals a second glycerolphosphate binding site in LtaS important for in vitro and in vivo enzyme function. Conclusion: These results suggest a binding mode for the lipoteichoic acid chain during polymerization. Significance: The identified binding site in LtaS could become a target for antibiotic development. Lipoteichoic acid (LTA) is an important cell wall component required for proper cell growth in many Gram-positive bacteria. In Listeria monocytogenes, two enzymes are required for the synthesis of this polyglycerolphosphate polymer. The LTA primase LtaPLm initiates LTA synthesis by transferring the first glycerolphosphate (GroP) subunit onto the glycolipid anchor and the LTA synthase LtaSLm extends the polymer by the repeated addition of GroP subunits to the tip of the growing chain. Here, we present the crystal structures of the enzymatic domains of LtaPLm and LtaSLm. Although the enzymes share the same fold, substantial differences in the cavity of the catalytic site and surface charge distribution contribute to enzyme specialization. The eLtaSLm structure was also determined in complex with GroP revealing a second GroP binding site. Mutational analysis confirmed an essential function for this binding site and allowed us to propose a model for the binding of the growing chain. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|