9.B.447.  The 1-Acyl-sn-Glycerol-3-Phosphate Acyltransferase gamma (AGPAT3) Family 

Acylation of diverse carbohydrates occurs across all domains of life and can be catalysed by proteins with a membrane bound acyltransferase-3 (AT3) domain (PF01757) (Newman et al. 2023). In bacteria, these proteins are essential in processes including symbiosis, resistance to viruses and antimicrobials, and biosynthesis of antibiotics Evolutionary co-variance analysis has been used to build a computational model of the structure of a bacterial O-antigen modifying acetyltransferase, OafB. The resulting structure exhibited a novel fold for the AT3 domain, which molecular dynamics simulations demonstrated is stable in the membrane. The AT3 domain contains 10 transmembrane helices arranged to form a large cytoplasmic cavity lined by residues known to be essential for function. Further molecular dynamics simulations support a model in which the acyl-CoA donor spans the membrane through accessing a pore created by movement of an important loop capping the inner cavity, enabling OafB to present the acetyl group close to the likely catalytic resides on the extracytoplasmic surface. Limited but important interactions with the fused SGNH domain in OafB were identified, and modelling suggests this domain is mobile and can both accept acyl-groups from the AT3 domain and then reach beyond the membrane to access acceptor substrates. This new general model of AT3 function provides a framework for the development of inhibitors that could abrogate critical functions of bacterial pathogens (Newman et al. 2023).



Leung, D.W. (2001). The structure and functions of human lysophosphatidic acid acyltransferases. Front Biosci 6: D944-953.

Newman, K.E., S.N. Tindall, S.L. Mader, S. Khalid, G.H. Thomas, and M.W. Van Der Woude. (2023). A novel fold for acyltransferase-3 (AT3) proteins provides a framework for transmembrane acyl-group transfer. Elife 12:.

Prasad, S.S., A. Garg, and A.K. Agarwal. (2011). Enzymatic activities of the human AGPAT isoform 3 and isoform 5: localization of AGPAT5 to mitochondria. J Lipid Res 52: 451-462.


TC#NameOrganismal TypeExample

1-acyl-sn-glycerol-3-phosphate acyltransferase, gamma, AGPAT3, of 376 aas and 2 TMSs, N- and C-terminal.  It converts 1-acyl-sn-glycerol-3-phosphate (lysophosphatidic acid or LPA) into 1,2-diacyl-sn-glycerol-3-phosphate (phosphatidic acid or PA) by incorporating an acyl moiety at the sn-2 position of the glycerol backbone (Prasad et al. 2011).

AGPAT3 of Homo sapiens


Probable 1-acyl-sn-glycerol-3-phosphate acyltransferase 4 of 442 aas and 2 -  4 TMSs, one or two at residues 70 - 100 and one or two at residues 350 - 390.

Acyltransferase of Rosa chinensis


Putative acyl transferase of 615 aas and possibly 6 TMSs in a 2 (residues 30 - 70) + 4 (residues 310 - 410) TMS topology.

Acyltransferase of Malus domestica (apple)


1-acyl-sn-glycerol-3-phosphate acyltransferase 2 of 521 aas and possibly 4 TMSs, 2 at residues 30 - 70, and 2 at residues 310 - 410.

Acyl transferase of Senna tora


Uncharacterized protein of 518 aas and possibly 7 TMSs in a 5 TMS (residues 1 - 200) + 1 (at residue 350) + 1 (at residue 410) TMS topology.

UP of Blomia tropicalis


TC#NameOrganismal TypeExample