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).
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1-acyl-sn-glycerol-3-phosphate acyltransferase, gamma, AGPAT3, of 376 aas and 2 or 3 TMSs, (One N- and either one or two 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 3 TMSs, one at residues 70 - 100 and two at residues 350 - 390.
Acyltransferase of Rosa chinensis
Putative acyl transferase of 615 aas and possibly 4 or 6 TMSs in a 2 or 3 TMS (residues residues 10 - 130) + 2 or 3 TMS (residues 315 - 430) TMS topology. Each of these hydrophobic regions is followed by about 180 hydrophilic regions suggesting an internal duplication, each of about 300 residues in length.
Acyltransferase of Malus domestica (apple)
1-acyl-sn-glycerol-3-phosphate acyltransferase 2 of 521 aas and possibly 4 TMSs, 2 at residues 1 - 80, and 2 at residues 330 - 410. Comparison with kother members of the family suggests there could be from 2 - 4 TMSs in the two halves of the protein.
Acyl transferase of Senna tora
Uncharacterized protein of 518 aas and possibly 4 TMSs in a 2 TMS (residues 1 - 80) + 2 (at residues 330 and 410, respectively) for a proposed 4 TMS topology.
UP of Blomia tropicalis
Osmotin (Osm34) is of 245 aas and one N-terminal TMS. This protein, residues 4 - 229, is homologous to the central portion (residues 371 - 615) of 9.B.447.1.3 but not of the other members of this TC family.
Osm34 of Arabidopsis thaliana (Mouse-ear cress)