Palmitoyl protein hydrolase/thioesterases is an enzyme (EC 3.1.2.22) that removes
thioester
In organic chemistry, thioesters are organosulfur compounds with the functional group . They are analogous to carboxylate esters () with the sulfur in the thioester playing the role of the linking oxygen in the carboxylate ester, as implied by t ...
-linked fatty acyl groups such as
palmitate
Palmitic acid (hexadecanoic acid in IUPAC nomenclature) is a fatty acid with a 16-carbon chain. It is the most common saturated fatty acid found in animals, plants and microorganisms.Gunstone, F. D., John L. Harwood, and Albert J. Dijkstra. The Li ...
from modified cysteine residues in proteins or peptides during
lysosomal degradation. It
catalyzes
Catalysis () is the process of increasing the rate of a chemical reaction by adding a substance known as a catalyst (). Catalysts are not consumed in the reaction and remain unchanged after it. If the reaction is rapid and the catalyst recyc ...
the reaction
:palmitoyl
rotein+ H
2O
palmitate + protein
This enzyme belongs to the family of
hydrolases, specifically those acting on
thioester
In organic chemistry, thioesters are organosulfur compounds with the functional group . They are analogous to carboxylate esters () with the sulfur in the thioester playing the role of the linking oxygen in the carboxylate ester, as implied by t ...
bonds. The
systematic name is palmitoyl
roteinhydrolase. Other names in common use include palmitoyl-protein thioesterase, and palmitoyl-(protein) hydrolase. This enzyme participates in
fatty acid elongation in mitochondria
Fatty is a derogatory term for someone who is obese. It may refer also to:
People
* Mai Fatty, Gambian politician
* Roscoe Arbuckle (1887–1933), American actor and comedian
* Fatty Briody (1858–1903), American Major League Baseball player
* ...
.
Neuronal ceroid lipofuscinoses
Neuronal ceroid lipofuscinosis is the general name for a family of at least eight genetically separate neurodegenerative lysosomal storage diseases that result from excessive accumulation of lipopigments (lipofuscin) in the body's tissues. These l ...
(NCL) represent a group of encephalopathies that occur in 1 in 12,500 children. Mutations in the palmitoyl protein thioesterase gene causing infantile neuronal ceroid lipofuscinosis.
The most common mutation results in intracellular accumulation of the polypeptide and undetectable enzyme activity in the brain. Direct sequencing of cDNAs derived from brain RNA of INCL patients has shown a mis-sense transversion of A to T at nucleotide position 364, which results in substitution of Trp for Arg at position 122 in the protein - Arg 122 is immediately adjacent to a lipase consensus sequence that contains the putative active site Ser of PPT. The occurrence of this and two other independent mutations in the PPT gene strongly suggests that defects in this gene cause INCL.
Examples
Human proteins containing this domain include:
Structural studies
As of late 2007, 4
structures have been solved for this class of enzymes, with
PDB accession codes , , , and .
See also
*
palmitoyl
Palmitoylation is the covalent attachment of fatty acids, such as palmitic acid, to cysteine (''S''-palmitoylation) and less frequently to serine and threonine (''O''-palmitoylation) residues of proteins, which are typically membrane proteins ...
*
Acyl-protein thioesterase
Acyl-protein thioesterases are enzymes that cleave off lipid modifications on proteins, located on the sulfur atom of cysteine residues linked via a thioester bond. Acyl-protein thioesterases are part of the α/β hydrolase superfamily of protein ...
s
References
Further reading
*
*
*
External links
*
GeneReviews/NCBI/NIH/UW entry on Neuronal Ceroid-Lipofuscinoses
EC 3.1.2
Enzymes of known structure
Peripheral membrane proteins
{{3.1-enzyme-stub