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Glycosyltransferase Family 38
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- Author: ^^^Warren Wakarchuk^^^
- Responsible Curator: ^^^Warren Wakarchuk^^^
Glycosyltransferase Family GT38 | |
Clan | GT-B |
Mechanisn | inverting |
Active site residues | known |
CAZy DB link | |
https://www.cazy.org/GT38.html |
Substrate specificities
Members of GT-38 are the bacterial polysialyltransferases (polySTs), which catalyze the addition of sialic acids from the activated sugar donor, CMP-sialic acid (CMP-Neu5Ac), to the nonreducing end of the growing polySia chain (PMID: 7972078 Cho and Troy 1994; Nakayama and Fukuda 1996). These enzymes build the polymer as a capsular polysaccharide on a specialized poly-β-KDO modified lyso-phosphatidyl glycerol anchor in the membrane of Gram negative bacteria [1]. . Bacterial polySia capsules exist in three different flavours: Escherichia coli K1, Neisseria meningitidis serotype B, Moraxella nonliquefaciens, and Mannheimia haemolytica A2 synthesize α-2,8-linked polySia whereas N. meningitidis serotype C produces a α-2,9-linked polymer and E. coli K92 produces polymers with alternating α-2,8 and α-2,9 linkages PMID: 10052589 PMID: 1898915 PMID: 64575. The molecular mimicry of these bacterial polySia capsules represents an elegant strategy to evade the host’s immune recognition since they are not considered as foreign. In addition, they confer a physical barrier protecting the pathogen from killing by the complement system PMID: 8884739.
Kinetics and Mechanism
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Catalytic Residues
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Three-dimensional structures
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Family Firsts
- First stereochemistry determination
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- First catalytic nucleophile identification
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- First general acid/base residue identification
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- First 3-D structure
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References
- Willis LM, Stupak J, Richards MR, Lowary TL, Li J, and Whitfield C. (2013). Conserved glycolipid termini in capsular polysaccharides synthesized by ATP-binding cassette transporter-dependent pathways in Gram-negative pathogens. Proc Natl Acad Sci U S A. 2013;110(19):7868-73. DOI:10.1073/pnas.1222317110 |
- Cantarel BL, Coutinho PM, Rancurel C, Bernard T, Lombard V, and Henrissat B. (2009). The Carbohydrate-Active EnZymes database (CAZy): an expert resource for Glycogenomics. Nucleic Acids Res. 2009;37(Database issue):D233-8. DOI:10.1093/nar/gkn663 |
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Davies, G.J. and Sinnott, M.L. (2008) Sorting the diverse: the sequence-based classifications of carbohydrate-active enzymes. The Biochemist, vol. 30, no. 4., pp. 26-32. Download PDF version.
- Lizak C, Worrall LJ, Baumann L, Pfleiderer MM, Volkers G, Sun T, Sim L, Wakarchuk W, Withers SG, and Strynadka NCJ. (2017). X-ray crystallographic structure of a bacterial polysialyltransferase provides insight into the biosynthesis of capsular polysialic acid. Sci Rep. 2017;7(1):5842. DOI:10.1038/s41598-017-05627-z |
- Lindhout T, Bainbridge CR, Costain WJ, Gilbert M, and Wakarchuk WW. (2013). Biochemical characterization of a polysialyltransferase from Mannheimia haemolytica A2 and comparison to other bacterial polysialyltransferases. PLoS One. 2013;8(7):e69888. DOI:10.1371/journal.pone.0069888 |
- Willis LM, Gilbert M, Karwaski MF, Blanchard MC, and Wakarchuk WW. (2008). Characterization of the alpha-2,8-polysialyltransferase from Neisseria meningitidis with synthetic acceptors, and the development of a self-priming polysialyltransferase fusion enzyme. Glycobiology. 2008;18(2):177-86. DOI:10.1093/glycob/cwm126 |
- Cho JW and Troy FA 2nd. (1994). Polysialic acid engineering: synthesis of polysialylated neoglycosphingolipids by using the polysialyltransferase from neuroinvasive Escherichia coli K1. Proc Natl Acad Sci U S A. 1994;91(24):11427-31. DOI:10.1073/pnas.91.24.11427 |
- Puente-Polledo L, Reglero A, González-Clemente C, Rodríguez-Aparicio LB, and Ferrero MA. (1998). Biochemical conditions for the production of polysialic acid by Pasteurella haemolytica A2. Glycoconj J. 1998;15(9):855-61. DOI:10.1023/a:1006902931032 |
- Devi SJ, Schneerson R, Egan W, Vann WF, Robbins JB, and Shiloach J. (1991). Identity between polysaccharide antigens of Moraxella nonliquefaciens, group B Neisseria meningitidis, and Escherichia coli K1 (non-O acetylated). Infect Immun. 1991;59(2):732-6. DOI:10.1128/iai.59.2.732-736.1991 |
- Glode MP, Robbins JB, Liu TY, Gotschlich EC, Orskov I, and Orskov F. (1977). Cross-antigenicity and immunogenicity between capsular polysaccharides of group C Neisseria meningitidis and of Escherichia coli K92. J Infect Dis. 1977;135(1):94-104. DOI:10.1093/infdis/135.1.94 |