Lysophospholipase-like 1 is a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...

in humans that is encoded by the LYPLAL1

gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...

. The protein is a α/β-hydrolase of uncharacterized

metabolic Metabolism (, from ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run cellular processes; the ...

function.

Genome-wide association studies In genomics, a genome-wide association study (GWA study, or GWAS), is an observational study of a genome-wide set of genetic variants in different individuals to see if any variant is associated with a trait. GWA studies typically focus on assoc ...

in humans have linked the gene to

fat distribution Human body shape is a complex phenomenon with sophisticated detail and function. The general shape or figure of a person is defined mainly by the molding of skeletal structures, as well as the distribution of muscles and fat. Skeletal structure ...

and waist-to-hip ratio. The protein's enzymatic function is unclear. LYPLAL1 was reported to act as a

triglyceride lipase The enzyme triacylglycerol lipase (also triglyceride lipase, EC 3.1.1.3;systematic name triacylglycerol acylhydrolase) catalyses the hydrolysis of ester linkages of triglycerides: : triacylglycerol + H2O diacylglycerol + a carboxylate These l ...

adipose tissue Adipose tissue (also known as body fat or simply fat) is a loose connective tissue composed mostly of adipocytes. It also contains the stromal vascular fraction (SVF) of cells including preadipocytes, fibroblasts, Blood vessel, vascular endothel ...

and another study suggested that the protein may play a role in the depalmitoylation of

calcium-activated potassium channel Calcium-activated potassium channels are potassium channels gated by calcium, or that are structurally or phylogenetically related to calcium gated channels. They were first discovered in 1958 by Gardos who saw that calcium levels inside of a cell ...

s. However, LYPLAL1 does not depalmitoylate the

oncogene An oncogene is a gene that has the potential to cause cancer. In tumor cells, these genes are often mutated, or expressed at high levels.

Ras and a

structural A structure is an arrangement and organization of interrelated elements in a material object or system, or the object or system so organized. Material structures include man-made objects such as buildings and machines and natural objects such as ...

and

enzymatic An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as produc ...

study concluded that LYPLAL1 is generally unable to act as a lipase and is instead an

esterase In biochemistry, an esterase is a class of enzyme that splits esters into an acid and an alcohol in a chemical reaction with water called hydrolysis (and as such, it is a type of hydrolase). A wide range of different esterases exist that differ ...

that prefers short-chain substrates, such as

acetyl group In organic chemistry, an acetyl group is a functional group denoted by the chemical formula and the structure . It is sometimes represented by the symbol Ac (not to be confused with the element actinium). In IUPAC nomenclature, an acetyl grou ...

s. Structural comparisons have suggested that LYPLAL1 might be a protein deacetylase, but this has not been experimentally tested.

Relationship to acyl-protein thioesterases

Sequence conservation In evolutionary biology, conserved sequences are identical or similar sequences in nucleic acids (DNA and RNA) or proteins across species ( orthologous sequences), or within a genome ( paralogous sequences), or between donor and receptor taxa ( ...

and

structural homology A protein superfamily is the largest grouping (clade) of proteins for which common ancestry can be inferred (see homology). Usually this common ancestry is inferred from structural alignment and mechanistic similarity, even if no sequence simila ...

suggest a close relationship of LYPLAL1 proteins to

acyl-protein thioesterase Acyl-protein thioesterases are enzymes that cleave off Lipid-anchored protein, lipid Post-translational modification, modifications on proteins, located on the sulfur atom of cysteine residues linked via a thioester bond. Acyl-protein thioesterase ...

s, and, therefore, it has been suggested that LYPLAL1 might be the third human acyl-protein thioesterase. However, the major structural difference between both

protein families A protein family is a group of evolutionarily related proteins. In many cases, a protein family has a corresponding gene family, in which each gene encodes a corresponding protein with a 1:1 relationship. The term "protein family" should not be c ...

has been established in the hydrophobic substrate binding tunnel, which has been identified in human acyl-protein thioesterases 1 and 2, as well as in ''Zea mays'' acyl-protein thioesterase 2. In LYPLAL1, this tunnel is closed due to a different loop conformation, changing the enzyme's

substrate Substrate may refer to: Physical layers *Substrate (biology), the natural environment in which an organism lives, or the surface or medium on which an organism grows or is attached ** Substrate (aquatic environment), the earthy material that exi ...

specificity to short acyl chains. LYLPLAL1 tunnel

Relationship to acyl-protein thioesterases

References

Further reading