PMID- 10781062
OWN - NLM
STAT- MEDLINE
DCOM- 20000524
LR  - 20230331
IS  - 0027-8424 (Print)
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Linking)
VI  - 97
IP  - 9
DP  - 2000 Apr 25
TI  - The crystal structure of palmitoyl protein thioesterase 1 and the molecular basis 
      of infantile neuronal ceroid lipofuscinosis.
PG  - 4573-8
AB  - 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.
FAU - Bellizzi, J J 3rd
AU  - Bellizzi JJ 3rd
AD  - Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 
      14853, USA.
FAU - Widom, J
AU  - Widom J
FAU - Kemp, C
AU  - Kemp C
FAU - Lu, J Y
AU  - Lu JY
FAU - Das, A K
AU  - Das AK
FAU - Hofmann, S L
AU  - Hofmann SL
FAU - Clardy, J
AU  - Clardy J
LA  - eng
SI  - PDB/1EH5
SI  - PDB/1EI9
GR  - R01 CA059021/CA/NCI NIH HHS/United States
GR  - R37 NS036867/NS/NINDS NIH HHS/United States
GR  - R01 NS035323/NS/NINDS NIH HHS/United States
GR  - NS 35323/NS/NINDS NIH HHS/United States
GR  - CA59021/CA/NCI NIH HHS/United States
GR  - P41 RR001646/RR/NCRR NIH HHS/United States
GR  - NS36867/NS/NINDS NIH HHS/United States
GR  - R01 NS036867/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - EC 3.1.2.- (Thiolester Hydrolases)
RN  - EC 3.1.2.14 (oleoyl-(acyl-carrier-protein) hydrolase)
RN  - EC 3.1.2.22 (palmitoyl-protein thioesterase)
SB  - IM
MH  - Amino Acid Sequence
MH  - Amino Acid Substitution
MH  - Crystallography, X-Ray
MH  - Humans
MH  - Infant
MH  - Models, Molecular
MH  - Molecular Sequence Data
MH  - Neuronal Ceroid-Lipofuscinoses/*enzymology/*genetics
MH  - Protein Folding
MH  - Protein Structure, Secondary
MH  - Thiolester Hydrolases/*chemistry/deficiency/genetics
PMC - PMC18274
EDAT- 2000/04/26 09:00
MHDA- 2000/06/08 09:00
PMCR- 2000/10/25
CRDT- 2000/04/26 09:00
PHST- 2000/04/26 09:00 [pubmed]
PHST- 2000/06/08 09:00 [medline]
PHST- 2000/04/26 09:00 [entrez]
PHST- 2000/10/25 00:00 [pmc-release]
AID - 080508097 [pii]
AID - 5080 [pii]
AID - 10.1073/pnas.080508097 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2000 Apr 25;97(9):4573-8. doi: 10.1073/pnas.080508097.