Glycosyltransferase Family 138

This page is currently under construction. This means that the Responsible Curator has deemed that the page's content is not quite up to CAZypedia's standards for full public consumption. All information should be considered to be under revision and may be subject to major changes.

• Author: Wei Peng
• Responsible Curator: Kim Orth

---

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

Substrate specificities

GT138 family of glycosyltransferase is exemplified by AvrB, a Fido protein (Fig. 1A) [1]. 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 modify the host protein RIN4 and causes the programmed cell death (namely hypersensitive response) [1, 2].

Kinetics and Mechanism

AvrB contains a Fido domain [3, 4] (Fig. 1A), different from other known glycosyltransferases containing folds of GT-A, GT-B, GT-C, lysozyme-type, GT101, and GT108 [5, 6, 7, 8] (Fig. 1B). Interestingly, Fido proteins can also be enzymes with activities of AMPylation [9], phosphorylation [10], UMPylation [11], and phosphocholination [12, 13]. Hence, AvrB is a unique Fido protein that functions as a glycosyltransferase.

Figure 1. Glycosyltransferase folds. (A) Fido fold (left [4]) 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.

The rhamnosylation reaction catalyzed by AvrB does not require divalent cations (e.g., Mg²⁺) [1]. In the reaction, rhamnose is directly transferred to the side chain of a threonine of RIN4, T166 (Fig. 2) [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. AvrB contains a large internal domain between helix α2 and helix α3 (Fig. 1A) [1, 3, 4, 14]. AvrB shares similar structural features with other Fido proteins despite the primary sequences are divergent [4].

Family Firsts

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

The first structure of GT138 family is AvrB [3]. A few AvrB structures are available to reveal the catalysis mechanisms [1, 3, 14]

References

Error fetching PMID 38354245:
Error fetching PMID 19503829:
Error fetching PMID 19039103:
Error fetching PMID 24141193:
Error fetching PMID 22504181:
Error fetching PMID 21822290:
Error fetching PMID 23572077:
Error fetching PMID 35536922:
Error fetching PMID 18518825:
Error fetching PMID 25023666:
Error fetching PMID 11955429:
Error fetching PMID 15016364:
Error fetching PMID 17397263:

8. 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 |