NlpC/P60 superfamily papain-like enzymes play important roles in all kingdoms
of life. Characterized members of this superfamily have diverse enzymatic
functions, such as peptidases, amidases, transglutaminases and
acetyltransferases. This divergent superfamily consists of four main families:
P60-like, AcmB/LytN-like (see <PDOC50911>), YaeF/YiiX-like, and LRAT-like. The
latter two families were predicted to contain a conserved catalytic triad
(Cys, His and a polar third residue) in a circularly permuted catalytic domain
where the relative positions of the cysteine and histidine/polar residue are
swapped in the primary sequence such that the catalytic cysteine is located
near the C-terminus, instead of at the N-terminus [1].
The NlpC/P60 LRAT-type family includes lecithin-retinol acyltransferase
(LRAT), nematode developmental regulator Egl-26, class II tumor suppressor
H-rev107 and proteins from poxviruses and animal positive-strand RNA viruses,
which share a common catalytic domain fold and the unconventional active site.
Several members of the NlpC/P60 LRAT-type family are able to act as
transferases/esterases utilizing glycerophospholipids as acyl donors
[1,2,3,4,5].
The basic structural motif of the LRAT domain is composed of a four-strand
antiparallel β-sheet and three α-helices (see <PDB:4DPZ>). The longest
α-helix (α3) 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
α3. This arrangement defines the active site location, which is embedded
into a well defined groove formed by the extended loops between β1-β2,
β3-β4, and the N-terminus of the α3 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 β2 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 β3 strand. The Cys residue was shown to act as a nucleophile
and form a covalent thiol-acyl intermediate in the catalytic process [6,7,8].
The profile we developed covers the entire LRAT domain.
PROSITE is copyrighted by the SIB Swiss Institute of Bioinformatics and
distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives
(CC BY-NC-ND 4.0) License, see