InterPro domain: IPR007053

This domain (LRAT domain) is found in a variety of proteins, including lecithin retinol acyltransferase (LRAT), HRAS-like suppressors (HRASLS1-5) and proteins FAM84A and FAM84B. Acyltransferase LRAT is the main enzyme that catalyzes vitamin A esterification [ 1 ]. HRASLS enzymes are also referred to as LRAT-like proteins because of their sequence homology to LRAT [ 2 ].

The basic structural motif of the LRAT domain is composed of a four-strand antiparallel beta-sheet and three alpha-helices. The longest alpha-helix (alpha3) is packed against the beta-sheet, and the two other shorter alpha-helices are located on the sides. A highly conserved catalytic Cys, identified as the acylation site, is located near the N terminus of alpha3. This arrangement defines the active site location, which is embedded into a well defined groove formed by the extended loops between beta1-beta2, beta3-beta4, and the N terminus of the alpha3 helix. The side chain of the Cys is packed against a beta-sheet core of the domain, placing it in close proximity to a conserved His from the beta2 strand. The beta-sheet is spread open on one end allowing formation of a hydrogen bond between the His and the Cys. The third polar residue in this catalytic triad is a polar residue in the neighboring beta3 strand. The Cys residue was shown to act as a nucleophile and form a covalent thiol-acyl intermediate in the catalytic process [ 3 , 3 , 4 ].

1. Disruption of the lecithin:retinol acyltransferase gene makes mice more susceptible to vitamin A deficiency. J. Biol. Chem. 280, 40226-34
2. Structural Basis for the Acyltransferase Activity of Lecithin:Retinol Acyltransferase-like Proteins. J. Biol. Chem. 287, 23790-807
3. Structure/function relationships of adipose phospholipase A2 containing a cys-his-his catalytic triad. J. Biol. Chem. 287, 35260-74
4. Structural and functional characterization of tumor suppressors TIG3 and H-REV107. FEBS Lett 589, 1179-86