Lecithin retinol acyltransferase (LRAT) is a retinyl ester synthase, catalyzing the formation of fatty acid retinyl esters, a crucial step in the retinoid cycle []. It has been linked to early onset retinitis pigmentosa [].
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 []. HRASLS enzymes are also referred to as LRAT-like proteins because of their sequence homology to LRAT [].The basic structural motif of the LRAT domain is composed of a four-strand antiparallel β-sheet and three α-helices. The longest α-helix (alpha3) is packed against the β-sheet, and the two other shorter α-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 β-sheet core of the domain, placing it in close proximity to a conserved His from the beta2 strand. The β-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 [, , ].
