PDBsum entry 1eh5

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protein ligands links
Hydrolase PDB id
Protein chain
279 a.a. *
NDG ×2
Waters ×36
* Residue conservation analysis
PDB id:
Name: Hydrolase
Title: Crystal structure of palmitoyl protein thioesterase 1 comple palmitate
Structure: Palmitoyl protein thioesterase 1. Chain: a. Engineered: yes
Source: Bos taurus. Cattle. Organism_taxid: 9913. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108. Expression_system_cell: sf21 cells. Other_details: 10 l bioreactor
Biol. unit: Dimer (from PQS)
2.50Å     R-factor:   0.226     R-free:   0.270
Authors: J.J.Bellizzi Iii,J.Widom,C.Kemp,J.Y.Lu,A.K.Das,S.L.Hofmann,J
Key ref:
J.J.Bellizzi et al. (2000). The crystal structure of palmitoyl protein thioesterase 1 and the molecular basis of infantile neuronal ceroid lipofuscinosis. Proc Natl Acad Sci U S A, 97, 4573-4578. PubMed id: 10781062 DOI: 10.1073/pnas.080508097
18-Feb-00     Release date:   26-Apr-00    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P45478  (PPT1_BOVIN) -  Palmitoyl-protein thioesterase 1
306 a.a.
279 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.  - Palmitoyl-protein hydrolase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Palmitoyl-[protein] + H2O = palmitate + [protein]
+ H(2)O
Bound ligand (Het Group name = PLM)
matches with 94.44% similarity
+ [protein]
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     extracellular region   8 terms 
  Biological process     membrane raft organization   18 terms 
  Biochemical function     hydrolase activity     3 terms  


    Key reference    
DOI no: 10.1073/pnas.080508097 Proc Natl Acad Sci U S A 97:4573-4578 (2000)
PubMed id: 10781062  
The crystal structure of palmitoyl protein thioesterase 1 and the molecular basis of infantile neuronal ceroid lipofuscinosis.
J.J.Bellizzi, J.Widom, C.Kemp, J.Y.Lu, A.K.Das, S.L.Hofmann, J.Clardy.
Mutations in palmitoyl-protein thioesterase 1 (PPT1), a lysosomal enzyme that removes fatty acyl groups from cysteine residues in modified proteins, cause the fatal inherited neurodegenerative disorder infantile neuronal ceroid lipofuscinosis. The accumulation of undigested substrates leads to the formation of neuronal storage bodies that are associated with the clinical symptoms. Less severe forms of PPT1 deficiency have been found recently that are caused by a distinct set of PPT1 mutations, some of which retain a small amount of thioesterase activity. We have determined the crystal structure of PPT1 with and without bound palmitate by using multiwavelength anomalous diffraction phasing. The structure reveals an alpha/beta-hydrolase fold with a catalytic triad composed of Ser115-His289-Asp233 and provides insights into the structural basis for the phenotypes associated with PPT1 mutations.
  Selected figure(s)  
Figure 3.
Fig. 3. Active site of PPT1. (A) The active site of native PPT1. A water molecule occupies the oxyanion hole, hydrogen-bonded to Ser115, Met41, and Gln116. The solvent-flattened multiwavelength anomalous diffraction electron density with experimental phases is superimposed on the model, contoured at 1.4 . (B) The active site of the PPT1/palmitate complex. A simulated annealing F[o]-F[c] map, generated by using CNS (24) with Ser115 and palmitate omitted from the calculation, is shown contoured at 1.5 .
Figure 5.
Fig. 5. NCL mutations in PPT1. (A) Sites of clinical NCL mutations in PPT1 are mapped onto the peptide backbone. INCL mutations are displayed in red, a mutation causing LINCL symptoms is in blue, and JNCL mutations are in green. (B) The most common INCL mutation (Arg122Trp) leads to the loss of three hydrogen bonds and a steric and polarity mismatch with the surrounding residues, resulting in misfolded protein. (C) The Gln177Glu mutation is predicted to cause the loss of hydrogen bonds to Ala171 and Ala183, two residues that contact palmitate. This mutation results in a less severe phenotype that is clinically indistinguishable from classical LINCL. (D) Two mutations on 1 lead to JNCL. Trp75Pro may alter the beginning of 1 due to the conformational restraints on Pro, and Asp79Glu loses hydrogen bonds to Cys45 and Ile72.
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20680390 A.L.Getty, and D.A.Pearce (2011).
Interactions of the proteins of neuronal ceroid lipofuscinosis: clues to function.
  Cell Mol Life Sci, 68, 453-474.  
21333648 M.Lazniewski, K.Steczkiewicz, L.Knizewski, I.Wawer, and K.Ginalski (2011).
Novel transmembrane lipases of alpha/beta hydrolase fold.
  FEBS Lett, 585, 870-874.  
20346914 G.Dawson, C.Schroeder, and P.E.Dawson (2010).
Palmitoyl:protein thioesterase (PPT1) inhibitors can act as pharmacological chaperones in infantile Batten disease.
  Biochem Biophys Res Commun, 395, 66-69.  
19440452 N.E.Muzaffar, and D.A.Pearce (2008).
Analysis of NCL Proteins from an Evolutionary Standpoint.
  Curr Genomics, 9, 115-136.  
17565660 A.Lyly, C.von Schantz, T.Salonen, O.Kopra, J.Saarela, M.Jauhiainen, A.Kyttälä, and A.Jalanko (2007).
Glycosylation, transport, and complex formation of palmitoyl protein thioesterase 1 (PPT1)--distinct characteristics in neurons.
  BMC Cell Biol, 8, 22.  
16452138 A.J.Hickey, H.L.Chotkowski, N.Singh, J.G.Ault, C.A.Korey, M.E.MacDonald, and R.L.Glaser (2006).
Palmitoyl-protein thioesterase 1 deficiency in Drosophila melanogaster causes accumulation of abnormal storage material and reduced life span.
  Genetics, 172, 2379-2390.  
16897798 B.M.Harvey, H.Hong, M.A.Jones, Z.A.Hughes-Thomas, R.M.Goss, M.L.Heathcote, V.M.Bolanos-Garcia, W.Kroutil, J.Staunton, P.F.Leadlay, and J.B.Spencer (2006).
Evidence that a novel thioesterase is responsible for polyketide chain release during biosynthesis of the polyether ionophore monensin.
  Chembiochem, 7, 1435-1442.  
16969373 J.W.Giraldes, D.L.Akey, J.D.Kittendorf, D.H.Sherman, J.L.Smith, and R.A.Fecik (2006).
Structural and mechanistic insights into polyketide macrolactonization from polyketide-based affinity labels.
  Nat Chem Biol, 2, 531-536.
PDB codes: 2h7x 2h7y
16962139 S.Bencharit, C.C.Edwards, C.L.Morton, E.L.Howard-Williams, P.Kuhn, P.M.Potter, and M.R.Redinbo (2006).
Multisite promiscuity in the processing of endogenous substrates by human carboxylesterase 1.
  J Mol Biol, 363, 201-214.
PDB codes: 2dqy 2dqz 2dr0 2h7c
15672447 M.Y.Porter, M.Turmaine, and S.E.Mole (2005).
Identification and characterization of Caenorhabditis elegans palmitoyl protein thioesterase1.
  J Neurosci Res, 79, 836-848.  
15965709 S.E.Mole, R.E.Williams, and H.H.Goebel (2005).
Correlations between genotype, ultrastructural morphology and clinical phenotype in the neuronal ceroid lipofuscinoses.
  Neurogenetics, 6, 107-126.  
14997549 I.Hudáky, Z.Gáspári, O.Carugo, M.Cemazar, S.Pongor, and A.Perczel (2004).
Vicinal disulfide bridge conformers by experimental methods and by ab initio and DFT molecular computations.
  Proteins, 55, 152-168.  
15075260 S.K.Cho, and S.L.Hofmann (2004).
pdf1, a palmitoyl protein thioesterase 1 Ortholog in Schizosaccharomyces pombe: a yeast model of infantile Batten disease.
  Eukaryot Cell, 3, 302-310.  
14629778 C.A.Korey, and M.E.MacDonald (2003).
An over-expression system for characterizing Ppt1 function in Drosophila.
  BMC Neurosci, 4, 30.  
12483688 L.Ahtiainen, O.P.Van Diggelen, A.Jalanko, and O.Kopra (2003).
Palmitoyl protein thioesterase 1 is targeted to the axons in neurons.
  J Comp Neurol, 455, 368-377.  
12724517 M.Cemazar, S.Zahariev, J.J.Lopez, O.Carugo, J.A.Jones, P.J.Hore, and S.Pongor (2003).
Oxidative folding intermediates with nonnative disulfide bridges between adjacent cysteine residues.
  Proc Natl Acad Sci U S A, 100, 5754-5759.  
11755680 M.C.Hunt, and S.E.Alexson (2002).
The role Acyl-CoA thioesterases play in mediating intracellular lipid metabolism.
  Prog Lipid Res, 41, 99.  
12005429 S.D.Bruner, T.Weber, R.M.Kohli, D.Schwarzer, M.A.Marahiel, C.T.Walsh, and M.T.Stubbs (2002).
Structural basis for the cyclization of the lipopeptide antibiotic surfactin by the thioesterase domain SrfTE.
  Structure, 10, 301-310.
PDB code: 1jmk
12220180 Z.Zhuang, F.Song, W.Zhang, K.Taylor, A.Archambault, D.Dunaway-Mariano, J.Dong, and P.R.Carey (2002).
Kinetic, Raman, NMR, and site-directed mutagenesis studies of the Pseudomonas sp. strain CBS3 4-hydroxybenzoyl-CoA thioesterase active site.
  Biochemistry, 41, 11152-11160.  
11723391 H.M.Mitchison, and S.E.Mole (2001).
Neurodegenerative disease: the neuronal ceroid lipofuscinoses (Batten disease).
  Curr Opin Neurol, 14, 795-803.  
11752428 S.C.Tsai, L.J.Miercke, J.Krucinski, R.Gokhale, J.C.Chen, P.G.Foster, D.E.Cane, C.Khosla, and R.M.Stroud (2001).
Crystal structure of the macrocycle-forming thioesterase domain of the erythromycin polyketide synthase: versatility from a unique substrate channel.
  Proc Natl Acad Sci U S A, 98, 14808-14813.
PDB code: 1kez
11080636 Y.Devedjiev, Z.Dauter, S.R.Kuznetsov, T.L.Jones, and Z.S.Derewenda (2000).
Crystal structure of the human acyl protein thioesterase I from a single X-ray data set to 1.5 A.
  Structure, 8, 1137-1146.
PDB code: 1fj2
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.