PMID- 19793631
OWN - NLM
STAT- MEDLINE
DCOM- 20101008
LR  - 20181201
IS  - 1872-7131 (Electronic)
IS  - 0387-7604 (Linking)
VI  - 32
IP  - 7
DP  - 2010 Aug
TI  - Structural basis of neuronal ceroid lipofuscinosis 1.
PG  - 524-30
LID - 10.1016/j.braindev.2009.08.010 [doi]
AB  - To elucidate the basis of neuronal ceroid lipofuscinosis 1 (CLN1) from the 
      viewpoint of enzyme structure, we constructed structural models of mutant 
      palmitoyl protein thioesterase 1 (PPT1) proteins using molecular modeling 
      software, jackal and TINKER. We classified the amino acid substitutions 
      responsible for CLN1 and divided them into two groups, groups 1 and 2, based on 
      the biochemical phenotype. Then, we examined the structural changes in the PPT1 
      protein for each group by calculating the solvent-accessible surface area (ASA) 
      and the number of atoms affected. Our results revealed that the structural 
      changes in group 1, which exhibits a complete deficiency of PPT1 activity, were 
      generally large and located in the core region of the enzyme molecule. In group 2 
      exhibiting residual PPT1 activity, the structural changes in PPT1 were smaller 
      and localized near the surface of the enzyme molecule. Coloring of affected atoms 
      based on the distances between those in the wild type and mutants revealed the 
      characteristic structural changes in the PPT1 protein geographically and 
      semi-quantitatively. Structural investigation provides us with a deeper insight 
      into the basis of CLN1.
CI  - Copyright 2009 Elsevier B.V. All rights reserved.
FAU - Ohno, Kazuki
AU  - Ohno K
AD  - NPO for the Promotion of Research on Intellectual Property Tokyo, Tokyo, Japan.
FAU - Saito, Seiji
AU  - Saito S
FAU - Sugawara, Kanako
AU  - Sugawara K
FAU - Suzuki, Toshihiro
AU  - Suzuki T
FAU - Togawa, Tadayasu
AU  - Togawa T
FAU - Sakuraba, Hitoshi
AU  - Sakuraba H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090929
PL  - Netherlands
TA  - Brain Dev
JT  - Brain & development
JID - 7909235
RN  - 0 (Membrane Proteins)
RN  - EC 3.1.2.- (Thiolester Hydrolases)
RN  - EC 3.1.2.22 (PPT1 protein, human)
SB  - IM
MH  - Amino Acid Substitution
MH  - Animals
MH  - Cattle
MH  - Humans
MH  - Membrane Proteins/*chemistry/genetics
MH  - *Models, Molecular
MH  - Neuronal Ceroid-Lipofuscinoses/*enzymology
MH  - Software
MH  - Thiolester Hydrolases
EDAT- 2009/10/02 06:00
MHDA- 2010/10/12 06:00
CRDT- 2009/10/02 06:00
PHST- 2009/06/02 00:00 [received]
PHST- 2009/08/13 00:00 [revised]
PHST- 2009/08/30 00:00 [accepted]
PHST- 2009/10/02 06:00 [entrez]
PHST- 2009/10/02 06:00 [pubmed]
PHST- 2010/10/12 06:00 [medline]
AID - S0387-7604(09)00243-5 [pii]
AID - 10.1016/j.braindev.2009.08.010 [doi]
PST - ppublish
SO  - Brain Dev. 2010 Aug;32(7):524-30. doi: 10.1016/j.braindev.2009.08.010. Epub 2009 
      Sep 29.