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Crossroads between Bacterial and Mammalian Glycosyltransferases.

Brockhausen I - Front Immunol (2014)

Bottom Line: Nevertheless, enzymatic properties, folding, substrate specificities, and catalytic mechanisms of these enzyme proteins may have significant similarity.A comparison is made here between mammalian and bacterial enzymes that synthesize epitopes found in mammalian glycoproteins, and those found in the O antigens of Gram-negative bacteria.The goals are to develop new strategies to reduce bacterial virulence and to synthesize vaccines and other biologically active glycan structures.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, Queen's University , Kingston, ON , Canada ; Department of Biomedical and Molecular Sciences, Queen's University , Kingston, ON , Canada.

ABSTRACT
Bacterial glycosyltransferases (GT) often synthesize the same glycan linkages as mammalian GT; yet, they usually have very little sequence identity. Nevertheless, enzymatic properties, folding, substrate specificities, and catalytic mechanisms of these enzyme proteins may have significant similarity. Thus, bacterial GT can be utilized for the enzymatic synthesis of both bacterial and mammalian types of complex glycan structures. A comparison is made here between mammalian and bacterial enzymes that synthesize epitopes found in mammalian glycoproteins, and those found in the O antigens of Gram-negative bacteria. These epitopes include Thomsen-Friedenreich (TF or T) antigen, blood group O, A, and B, type 1 and 2 chains, Lewis antigens, sialylated and fucosylated structures, and polysialic acids. Many different approaches can be taken to investigate the substrate binding and catalytic mechanisms of GT, including crystal structure analyses, mutations, comparison of amino acid sequences, NMR, and mass spectrometry. Knowledge of the protein structures and functions helps to design GT for specific glycan synthesis and to develop inhibitors. The goals are to develop new strategies to reduce bacterial virulence and to synthesize vaccines and other biologically active glycan structures.

No MeSH data available.


Biosynthesis of polysialic acids in E. coli using the ABC transporter pathway. The biosynthesis of homopolymeric O antigens (or capsules) is initiated at the cytosolic side of the inner membrane. Polysialic acids (PSA) of E. coli are proposed to be assembled in a processive fashion as shown, based on undecaprenol-phosphate. Membrane-associated polysialyltransferase (PST) transfers many units of sialic acid from CMP-sialic acid to the growing polysialic acid. The enzyme can act on a number of acceptor substrates to form repeated sialylα2–8 linkages. A termination reaction stops the growth of the long PSA chain. The PSA is then transported to the periplasmic space by the Wzm exporter, which is associated with the ATP-binding Wzt. Further processing occurs in the periplasm. The completed PSA is ligated to the core-lipid A and then translocated by export proteins to the outer membrane to serve as a highly charged and hydrophilic protective coat. Other homopolymeric O antigens such as poly-d-Mannose or poly-d-Rhamnose are processed in a similar fashion by the ABC transporter pathway.
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Figure 3: Biosynthesis of polysialic acids in E. coli using the ABC transporter pathway. The biosynthesis of homopolymeric O antigens (or capsules) is initiated at the cytosolic side of the inner membrane. Polysialic acids (PSA) of E. coli are proposed to be assembled in a processive fashion as shown, based on undecaprenol-phosphate. Membrane-associated polysialyltransferase (PST) transfers many units of sialic acid from CMP-sialic acid to the growing polysialic acid. The enzyme can act on a number of acceptor substrates to form repeated sialylα2–8 linkages. A termination reaction stops the growth of the long PSA chain. The PSA is then transported to the periplasmic space by the Wzm exporter, which is associated with the ATP-binding Wzt. Further processing occurs in the periplasm. The completed PSA is ligated to the core-lipid A and then translocated by export proteins to the outer membrane to serve as a highly charged and hydrophilic protective coat. Other homopolymeric O antigens such as poly-d-Mannose or poly-d-Rhamnose are processed in a similar fashion by the ABC transporter pathway.

Mentions: The less common homopolymeric O antigens, such as the d-Rha polymers of Pseudomonas aeruginosa (Pa) and the d-Man polymers of E. coli O9, are synthesized by the transfer of monosaccharides from nucleotide sugars to R-GlcNAc-PP-Und in a processive fashion in the ABC transporter-dependent pathway (Figure 3) (51). Some of the processive GTs can have multiple catalytic domains, e.g., Man-transferase WbdA. The entire O antigen is assembled on the cytosolic side, and terminated by termination reactions, e.g., methylation. This is followed by translocation of the large O-antigen-PP-Und by the Wzm exporter and the ATP-binding Wzt to the periplasm where it is further processed. The presence of wzm and wzt genes in the O antigen gene cluster would suggest that this pathway is operative.


Crossroads between Bacterial and Mammalian Glycosyltransferases.

Brockhausen I - Front Immunol (2014)

Biosynthesis of polysialic acids in E. coli using the ABC transporter pathway. The biosynthesis of homopolymeric O antigens (or capsules) is initiated at the cytosolic side of the inner membrane. Polysialic acids (PSA) of E. coli are proposed to be assembled in a processive fashion as shown, based on undecaprenol-phosphate. Membrane-associated polysialyltransferase (PST) transfers many units of sialic acid from CMP-sialic acid to the growing polysialic acid. The enzyme can act on a number of acceptor substrates to form repeated sialylα2–8 linkages. A termination reaction stops the growth of the long PSA chain. The PSA is then transported to the periplasmic space by the Wzm exporter, which is associated with the ATP-binding Wzt. Further processing occurs in the periplasm. The completed PSA is ligated to the core-lipid A and then translocated by export proteins to the outer membrane to serve as a highly charged and hydrophilic protective coat. Other homopolymeric O antigens such as poly-d-Mannose or poly-d-Rhamnose are processed in a similar fashion by the ABC transporter pathway.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4202792&req=5

Figure 3: Biosynthesis of polysialic acids in E. coli using the ABC transporter pathway. The biosynthesis of homopolymeric O antigens (or capsules) is initiated at the cytosolic side of the inner membrane. Polysialic acids (PSA) of E. coli are proposed to be assembled in a processive fashion as shown, based on undecaprenol-phosphate. Membrane-associated polysialyltransferase (PST) transfers many units of sialic acid from CMP-sialic acid to the growing polysialic acid. The enzyme can act on a number of acceptor substrates to form repeated sialylα2–8 linkages. A termination reaction stops the growth of the long PSA chain. The PSA is then transported to the periplasmic space by the Wzm exporter, which is associated with the ATP-binding Wzt. Further processing occurs in the periplasm. The completed PSA is ligated to the core-lipid A and then translocated by export proteins to the outer membrane to serve as a highly charged and hydrophilic protective coat. Other homopolymeric O antigens such as poly-d-Mannose or poly-d-Rhamnose are processed in a similar fashion by the ABC transporter pathway.
Mentions: The less common homopolymeric O antigens, such as the d-Rha polymers of Pseudomonas aeruginosa (Pa) and the d-Man polymers of E. coli O9, are synthesized by the transfer of monosaccharides from nucleotide sugars to R-GlcNAc-PP-Und in a processive fashion in the ABC transporter-dependent pathway (Figure 3) (51). Some of the processive GTs can have multiple catalytic domains, e.g., Man-transferase WbdA. The entire O antigen is assembled on the cytosolic side, and terminated by termination reactions, e.g., methylation. This is followed by translocation of the large O-antigen-PP-Und by the Wzm exporter and the ATP-binding Wzt to the periplasm where it is further processed. The presence of wzm and wzt genes in the O antigen gene cluster would suggest that this pathway is operative.

Bottom Line: Nevertheless, enzymatic properties, folding, substrate specificities, and catalytic mechanisms of these enzyme proteins may have significant similarity.A comparison is made here between mammalian and bacterial enzymes that synthesize epitopes found in mammalian glycoproteins, and those found in the O antigens of Gram-negative bacteria.The goals are to develop new strategies to reduce bacterial virulence and to synthesize vaccines and other biologically active glycan structures.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, Queen's University , Kingston, ON , Canada ; Department of Biomedical and Molecular Sciences, Queen's University , Kingston, ON , Canada.

ABSTRACT
Bacterial glycosyltransferases (GT) often synthesize the same glycan linkages as mammalian GT; yet, they usually have very little sequence identity. Nevertheless, enzymatic properties, folding, substrate specificities, and catalytic mechanisms of these enzyme proteins may have significant similarity. Thus, bacterial GT can be utilized for the enzymatic synthesis of both bacterial and mammalian types of complex glycan structures. A comparison is made here between mammalian and bacterial enzymes that synthesize epitopes found in mammalian glycoproteins, and those found in the O antigens of Gram-negative bacteria. These epitopes include Thomsen-Friedenreich (TF or T) antigen, blood group O, A, and B, type 1 and 2 chains, Lewis antigens, sialylated and fucosylated structures, and polysialic acids. Many different approaches can be taken to investigate the substrate binding and catalytic mechanisms of GT, including crystal structure analyses, mutations, comparison of amino acid sequences, NMR, and mass spectrometry. Knowledge of the protein structures and functions helps to design GT for specific glycan synthesis and to develop inhibitors. The goals are to develop new strategies to reduce bacterial virulence and to synthesize vaccines and other biologically active glycan structures.

No MeSH data available.