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, image from [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.

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 (image from [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 members

AvrB is the only well-studied member so far in the GT138 family [1].

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

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 |
2. Lee CC, Wood MD, Ng K, Andersen CB, Liu Y, Luginbühl P, Spraggon G, and Katagiri F. (2004). Crystal structure of the type III effector AvrB from Pseudomonas syringae. Structure. 2004;12(3):487-94. DOI:10.1016/j.str.2004.02.013 |
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 |
4. Varki A, Cummings RD, Esko JD, Stanley P, Hart GW, Aebi M, Mohnen D, Kinoshita T, Packer NH, Prestegard JH, Schnaar RL, and Seeberger PH. (2022). 2022. DOI:10.1101/9781621824213 |
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 |
6. Zhang H, Zhu F, Yang T, Ding L, Zhou M, Li J, Haslam SM, Dell A, Erlandsen H, and Wu H. (2014). The highly conserved domain of unknown function 1792 has a distinct glycosyltransferase fold. Nat Commun. 2014;5:4339. DOI:10.1038/ncomms5339 |
7. Sernee MF, Ralton JE, Nero TL, Sobala LF, Kloehn J, Vieira-Lara MA, Cobbold SA, Stanton L, Pires DEV, Hanssen E, Males A, Ward T, Bastidas LM, van der Peet PL, Parker MW, Ascher DB, Williams SJ, Davies GJ, and McConville MJ. (2019). A Family of Dual-Activity Glycosyltransferase-Phosphorylases Mediates Mannogen Turnover and Virulence in Leishmania Parasites. Cell Host Microbe. 2019;26(3):385-399.e9. DOI:10.1016/j.chom.2019.08.009 |
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 |
13. Mackey D, Holt BF 3rd, Wiig A, and Dangl JL. (2002). RIN4 interacts with Pseudomonas syringae type III effector molecules and is required for RPM1-mediated resistance in Arabidopsis. Cell. 2002;108(6):743-54. DOI:10.1016/s0092-8674(02)00661-x |
14. Desveaux D, Singer AU, Wu AJ, McNulty BC, Musselwhite L, Nimchuk Z, Sondek J, and Dangl JL. (2007). Type III effector activation via nucleotide binding, phosphorylation, and host target interaction. PLoS Pathog. 2007;3(3):e48. DOI:10.1371/journal.ppat.0030048 |