Glycosyltransferase Family 138

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• Author: Wei Peng
• Responsible Curator: Kim Orth

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Glycosyltransferase Family GT138
Clan	Fido fold
Mechanism	Inverting
Active site residues	Known
CAZy DB link
https://www.cazy.org/GT138.html

Family features

GT138 family of glycosyltransferase is exemplified by AvrB [1]. AvrB contains a Fido domain (Fig. 1A) [2, 3], different from other known glycosyltransferases containing folds of GT-A, GT-B, GT-C, lysozyme-type, GT101, and GT108 (Fig. 1B) [4, 5, 6, 7].

Interestingly, Fido proteins can also be enzymes with activities of AMPylation [8], phosphorylation [9], UMPylation [10], and phosphocholination [11, 12]. Hence, AvrB is a unique Fido protein that functions as a glycosyltransferase.

Figure 1. Glycosyltransferase folds. (A) Fido fold (left [3]) is found in diverse enzymes including AvrB (right), which is a distinct glycosyltransferase. (B) Other known glycosyltransferases contain folds of GT-A, GT-B, GT-C, lysozyme-type, GT101, and GT108. PDB codes are provided for representative structures.

Family members

AvrB is the only well-studied member so far in the GT138 family.

Substrate specificities

As a bacterial effector from the plant pathogen Pseudomonas syringae, AvrB utilizes host UDP-rhamnose (or dTDP-rhamnose in vitro) as a co-substrate to rhamnosylate the host protein RIN4 and causes the programmed cell death (namely hypersensitive response) [1, 13].

Kinetics and Mechanism

In the reaction, rhamnose is directly transferred to the side chain of a threonine of RIN4, T166 (Fig. 2) [1]. The rhamnosylation reaction catalyzed by AvrB does not require divalent cations (e.g., Mg²⁺) [1].

Figure 2. Catalysis mechanisms for RIN4 rhamnosylation by AvrB supported by crystal structures [1]. (A) AvrB bound with RIN4. (B) UDP-rhamnose bound with AvrB and RIN4. (C) Rhamnose transferred to T166 of RIN4. (D) Release of rhamnosylated RIN4.

Catalytic Residues

A threonine (T166) from the protein substrate directly attacks the rhamnose moiety in the co-substrate, UDP-rhamnose (Fig. 2) [1]. The threonine is close to a histidine and a threonine in AvrB, which may stabilize the acceptor. UDP-rhamnose is stabilized by a few residues in the pocket (Fig. 2) [1].

Three-dimensional structures

AvrB represents the prototype for glycosyltransferases of Fido fold [1]. AvrB contains a large internal domain between helix α2 and helix α3 (Fig. 1A) [1, 2, 3, 14]. AvrB shares similar structural features with other Fido proteins despite the primary sequences are divergent [3].

Family Firsts

The first member of GT138 family shown to be a glycosyltransferase is AvrB [1].

The first structure of GT138 family is AvrB [2]. A few AvrB structures are available to reveal the catalysis mechanisms [1, 2, 14]

References

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1. Peng W, Garcia N, Servage KA, Kohler JJ, Ready JM, Tomchick DR, Fernandez J, and Orth K. (2024). Pseudomonas effector AvrB is a glycosyltransferase that rhamnosylates plant guardee protein RIN4. Sci Adv. 2024;10(7):eadd5108. DOI:10.1126/sciadv.add5108 |
3. Kinch LN, Yarbrough ML, Orth K, and Grishin NV. (2009). Fido, a novel AMPylation domain common to fic, doc, and AvrB. PLoS One. 2009;4(6):e5818. DOI:10.1371/journal.pone.0005818 |
5. 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 |
8. Yarbrough ML, Li Y, Kinch LN, Grishin NV, Ball HL, and Orth K. (2009). AMPylation of Rho GTPases by Vibrio VopS disrupts effector binding and downstream signaling. Science. 2009;323(5911):269-72. DOI:10.1126/science.1166382 |
9. Castro-Roa D, Garcia-Pino A, De Gieter S, van Nuland NAJ, Loris R, and Zenkin N. (2013). The Fic protein Doc uses an inverted substrate to phosphorylate and inactivate EF-Tu. Nat Chem Biol. 2013;9(12):811-7. DOI:10.1038/nchembio.1364 |
10. Feng F, Yang F, Rong W, Wu X, Zhang J, Chen S, He C, and Zhou JM. (2012). A Xanthomonas uridine 5'-monophosphate transferase inhibits plant immune kinases. Nature. 2012;485(7396):114-8. DOI:10.1038/nature10962 |
11. Mukherjee S, Liu X, Arasaki K, McDonough J, Galán JE, and Roy CR. (2011). Modulation of Rab GTPase function by a protein phosphocholine transferase. Nature. 2011;477(7362):103-6. DOI:10.1038/nature10335 |
12. Campanacci V, Mukherjee S, Roy CR, and Cherfils J. (2013). Structure of the Legionella effector AnkX reveals the mechanism of phosphocholine transfer by the FIC domain. EMBO J. 2013;32(10):1469-77. DOI:10.1038/emboj.2013.82 |