LYPLAL1

Lysophospholipase-like 1 is a protein in humans that is encoded by the LYPLAL1 gene. ^[1] The protein is a α/β-hydrolase of uncharacterized metabolic function. Genome-wide association studies in humans have linked the gene to fat distribution^[2] and waist-to-hip ratio.^[3] The protein's enzymatic function is unclear. LYPLAL1 was reported to act as a triglyceride lipase in adipose tissue^[4] and another study suggested that the protein may play a role in the depalmitoylation of calcium-activated potassium channels.^[5] However, LYPLAL1 does not depalmitoylate the oncogene Ras^[6] and a structural and enzymatic study concluded that LYPLAL1 is generally unable to act as a lipase and is instead an esterase that prefers short-chain substrates, such as acetyl groups.^[7] Structural comparisons have suggested that LYPLAL1 might be a protein deacetylase, but this has not been experimentally tested.^[8]

Crystal structure of human LYPLAL1, PDB code 3u0v. Alpha helices are in red, beta strands in gold, catalytic site residues in black.
Identifiers
Symbol	Lysophospholipase-like protein 1
Pfam	PF02230
InterPro	IPR029058
CATH	3u0v
SCOP2	3u0v / SCOPe / SUPFAM
Available protein structures: Pfam   structures / ECOD   PDB RCSB PDB; PDBe; PDBj PDBsum structure summary

Relationship to acyl-protein thioesterases

Sequence conservation and structural homology suggest a close relationship of LYPLAL1 proteins to acyl-protein thioesterases, and, therefore, it has been suggested that LYPLAL1 might be the third human acyl-protein thioesterase.^[9] However, the major structural difference between both protein families has been established in the hydrophobic substrate binding tunnel, which has been identified in human acyl-protein thioesterases 1^[10] and 2,^[11] as well as in Zea mays acyl-protein thioesterase 2.^[12] In LYPLAL1, this tunnel is closed due to a different loop conformation, changing the enzyme's substrate specificity to short acyl chains.^[7]

Protein surface of human LYPLAL1 (PDB code 3u0v), showing electrostatic charges (red = negative, blue = positive, white = hydrophobic. On the right, the tunnel-closing loop is shown.