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EC Number

Catalytic Site Atlas

CSA LITERATURE entry for 1eh5

E.C. namepalmitoyl[protein] hydrolase
SpeciesBos taurus (Bovine)
E.C. Number (IntEnz)
CSA Homologues of 1eh51ei9,1exw,3gro,
CSA Entries With UniProtID P45478
CSA Entries With EC Number
PDBe Entry 1eh5
PDBSum Entry 1eh5
MACiE Entry 1eh5

Literature Report

IntroductionPalmitoyl-protein thioesterase I (PPT1) is a lysosomal enzyme which is implicated in the degredation of lipid modified proteins, removing fatty acid groups from cysteine residues. The accumulation of undisgested substrate when a mutant enzyme is present leads to the formation of neuronal storage bodies that are associated with the clinical symptoms of infantile ceroid lipofuscinosis.
MechansimPPT1 contains a catalytic triad composed of Ser115, His 289 and Asp233. Nucleophilic attack by Ser155 on the carbonyl of the substrate palmitate generates a enzyme-substrate tetrahedral intermediate where the main chain NH components of Met41 and Gln116 acts as hydrogen bond donors to stabilise the intermediate oxyanion. Proton donation and subsequent collapse of the intermediate forms an acyl-enzyme intermediate. This is then attacked by a nucleophilic water molcecule, generating a second anionic intermediate, followed by cleavage of the enzyme-acyl bond to generate the products.

Catalytic Sites for 1eh5

Annotated By Reference To The Literature - Site 1 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
SerA115115macie:sideChainThe residue is activated towards nucleophilic attack at the substrate by interaction with His 289, forming a tetrahedral intermediate.
HisA289289macie:sideChainThe residue acts as a base towards the nucleophilic Ser115. It is activated towards accepting a proton through hydrogen bonding to Asp233. The residue also acts as a proton donor to the initial anionic intermediate.In the free enzyme, the residue is hydrogen bonded to Ser115.
AspA233233macie:sideChainThe residue modifies the pH of the basic His 289 residue through hydrogen bonding.
MetA4141macie:mainChainAmideThe residue main chain NH component is involved in an oxyanion hole, stabilising the anionic tetrahedral intermediate.
GlnA116116macie:mainChainAmideThe residue main chain NH component is involved in an oxyanion hole, stabilising the anionic tetrahedral intermediate.

Literature References

Holmquist M.
Alpha/Beta-hydrolase fold enzymes: structures, functions and mechanisms.
Curr Protein Pept Sci 2000 1 209-235
PubMed: 12369917
Bellizzi JJ 3rd
The crystal structure of palmitoyl protein thioesterase 1 and the molecular basis of infantile neuronal ceroid lipofuscinosis.
Proc Natl Acad Sci U S A 2000 97 4573-4578
PubMed: 10781062