Glycosyltransferases

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• Author: Spencer Williams
• Responsible Curator: Spencer Williams

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Overview

Glycosyltransferases are enzymes that catalyze the formation of the glycosidic linkage to form a glycoside. These enzymes utilize 'activated' sugar phosphates as glycosyl donors, and catalyze glycosyl group transfer to a nucleophilic group, usually an alcohol. The product of glycosyl transfer may be an O-, N-, S-, or C-glycoside; the glycoside may be part of a monosaccharide glycoside, oligosaccharide, or polysaccharide ([1, 2, 3, 4, 5]).

Donors

Glycosyltransferases can utilize a range of donor species. Sugar mono- or diphosphonucleotides are sometimes termed Leloir donors (after Nobel prize winner, Luis Leloir); the corresponding enzymes are termed Leloir donors.

Glycosyltransferases that utilize non-nucleotide donors, which may be polyprenol pyrophosphates, polyprenol phosphates, sugar-1-phosphates, or sugar-1-pyrophosphates, are termed non-Leloir glycosyltransferases.

Mechanism

Glycosyltransferases catalyze the transfer of glycosyl groups to a nucleophilic acceptor with either retention or inversion of configuration at the anomeric centre. This allows the classification of glycosyltransferases as either retaining or inverting enzymes.

Inverting glycosyltransferases

Structural and kinetic data for inverting glycosyltransferases support a mechanism that proceeds through a single nucleophilic substitution step, facilitated by an enzymic general base catalyst. The transition state is believed to possess substantial oxocarbenium ion character.

3-D folds

A representative GT-A fold: SpsA from Bacillus subtilus, PDB code 1h7l [6]. The complex also contains two magnesium ions and a molecule of thymidine-5'-diphosphate. <jmol> <jmolApplet> <color>white</color> <frame>true</frame> <uploadedFileContents>1h7l.pdb</uploadedFileContents> <script>cpk off; wireframe off; cartoon; color cartoon powderblue; select ligand; wireframe 0.3; select MG; spacefill;set spin Y 10; spin on; set antialiasDisplay ON</script> </jmolApplet> </jmol> A representative GT-B fold: Bacteriophage T4 beta-glucosyltransferase, PDB code 1bgt [7]. <jmol> <jmolApplet> <color>white</color> <frame>true</frame> <uploadedFileContents>1h7l.pdb</uploadedFileContents> <script>cpk off; wireframe off; cartoon; color cartoon powderblue; select ligand; wireframe 0.3; select MG; spacefill;set spin Y 10; spin on; set antialiasDisplay ON</script> </jmolApplet> </jmol> Role of metals Common sugar nucleotide donors References Robert V. Stick and Spencer J. Williams. (2009) Carbohydrates. Elsevier Science. Lairson LL, Henrissat B, Davies GJ, and Withers SG. (2008). Glycosyltransferases: structures, functions, and mechanisms. Annu Rev Biochem. 2008;77:521-55. DOI:10.1146/annurev.biochem.76.061005.092322 | Coutinho PM, Deleury E, Davies GJ, and Henrissat B. (2003). An evolving hierarchical family classification for glycosyltransferases. J Mol Biol. 2003;328(2):307-17. DOI:10.1016/s0022-2836(03)00307-3 | Chapter 5: Coutinho PM, Rancurel C, Stam M, Bernard T, Couto FM, Danchin EGJ, Henrissat B. "Carbohydrate-active Enzymes Database: Principles and Classification of Glycosyltransferases." Campbell JA, Davies GJ, Bulone V, and Henrissat B. (1997). A classification of nucleotide-diphospho-sugar glycosyltransferases based on amino acid sequence similarities. Biochem J. 1997;326 ( Pt 3)(Pt 3):929-39. DOI:10.1042/bj3260929u | Claus-Wilhelm von der Lieth, Thomas Luetteke, and Martin Frank. (2010-01-19) Bioinformatics for Glycobiology and Glycomics: An Introduction. Wiley. Charnock SJ and Davies GJ. (1999). Structure of the nucleotide-diphospho-sugar transferase, SpsA from Bacillus subtilis, in native and nucleotide-complexed forms. Biochemistry. 1999;38(20):6380-5. DOI:10.1021/bi990270y | Vrielink A, Rüger W, Driessen HP, and Freemont PS. (1994). Crystal structure of the DNA modifying enzyme beta-glucosyltransferase in the presence and absence of the substrate uridine diphosphoglucose. EMBO J. 1994;13(15):3413-22. DOI:10.1002/j.1460-2075.1994.tb06646.x |