title: Structural and mechanistic insight into the Listeria monocytogenes two-enzyme lipoteichoic acid synthesis system.
abstract: 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 LtaP(Lm) initiates LTA synthesis by transferring the first glycerolphosphate (GroP) subunit onto the glycolipid anchor and the LTA synthase LtaS(Lm) 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 LtaP(Lm) and LtaS(Lm). 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 eLtaS(Lm) 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.
authors.affiliation: From the Section of Microbiology and MRC Centre for Molecular Bacteriology and Infection, and.
authors.forename: Ivan
authors.initials: I
authors.lastname: Campeotto
authors.affiliation: From the Section of Microbiology and MRC Centre for Molecular Bacteriology and Infection, and.
authors.forename: Matthew G
authors.initials: MG
authors.lastname: Percy
authors.affiliation: the Centre for Structural Biology, Imperial College London, London SW7 2AZ, United Kingdom.
authors.forename: James T
authors.initials: JT
authors.lastname: MacDonald
authors.affiliation: the Centre for Structural Biology, Imperial College London, London SW7 2AZ, United Kingdom.
authors.forename: Andreas
authors.initials: A
authors.lastname: Förster
authors.affiliation: the Centre for Structural Biology, Imperial College London, London SW7 2AZ, United Kingdom p.freemont@imperial.ac.uk.
authors.forename: Paul S
authors.initials: PS
authors.lastname: Freemont
authors.affiliation: From the Section of Microbiology and MRC Centre for Molecular Bacteriology and Infection, and a.grundling@imperial.ac.uk.
authors.forename: Angelika
authors.initials: A
authors.lastname: Gründling
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D020134:Catalytic Domain; D002473:Cell Wall / Q000737:chemistry* / Q000201:enzymology; D018360:Crystallography, X-Ray; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D005994:Glycerophosphates / Q000737:chemistry* / Q000378:metabolism; D008070:Lipopolysaccharides / Q000096:biosynthesis*; D008089:Listeria monocytogenes / Q000737:chemistry* / Q000145:classification / Q000201:enzymology; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D010802:Phylogeny; D011485:Protein Binding; D017510:Protein Folding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D055672:Static Electricity; D013682:Teichoic Acids / Q000096:biosynthesis*
chemical_list: D001426:Bacterial Proteins; D005994:Glycerophosphates; D008070:Lipopolysaccharides; D011994:Recombinant Proteins; D013682:Teichoic Acids; C009900:lipoteichoic acid
keywords: Bacteria; Cell Wall; Enzyme Catalysis; LTA Synthesis; Lipid; Protein Structure