PMID- 15960609
OWN - NLM
STAT- MEDLINE
DCOM- 20060126
LR  - 20240414
IS  - 1470-8728 (Electronic)
IS  - 0264-6021 (Print)
IS  - 0264-6021 (Linking)
VI  - 391
IP  - Pt 2
DP  - 2005 Oct 15
TI  - Mutations in dopachrome tautomerase (Dct) affect eumelanin/pheomelanin synthesis, 
      but do not affect intracellular trafficking of the mutant protein.
PG  - 249-59
AB  - Dopachrome tautomerase (Dct) is a type I membrane protein and an important 
      regulatory enzyme that plays a pivotal role in the biosynthesis of melanin and in 
      the rapid metabolism of its toxic intermediates. Dct-mutant melanocytes carrying 
      the slaty or slaty light mutations were derived from the skin of newborn congenic 
      C57BL/6J non-agouti black mice and were used to study the effect(s) of these 
      mutations on the intracellular trafficking of Dct and on the pigmentation of the 
      cells. Dct activity is 3-fold lower in slaty cells compared with non-agouti black 
      melanocytes, whereas slaty light melanocytes have a surprisingly 28-fold lower 
      Dct activity. Homology modelling of the active site of Dct suggests that the 
      slaty mutation [R194Q (Arg194-->Gln)] is located in the active site and may alter 
      the ability of the enzyme to transform the substrate. Transmembrane prediction 
      methods indicate that the slaty light mutation [G486R (Gly486-->Arg)] may result 
      in the sliding of the transmembrane domain towards the N-terminus, thus 
      interfering with Dct function. Chemical analysis showed that both Dct mutations 
      increase pheomelanin and reduce eumelanin produced by melanocytes in culture. 
      Thus the enzymatic activity of Dct may play a role in determining whether the 
      eumelanin or pheomelanin pathway is preferred for pigment biosynthesis.
FAU - Costin, Gertrude-E
AU  - Costin GE
AD  - Pigment Cell Biology Section, Laboratory of Cell Biology, National Cancer 
      Institute, National Institutes of Health (NIH), Bethesda, MD 20892, USA.
FAU - Valencia, Julio C
AU  - Valencia JC
FAU - Wakamatsu, Kazumasa
AU  - Wakamatsu K
FAU - Ito, Shosuke
AU  - Ito S
FAU - Solano, Francisco
AU  - Solano F
FAU - Milac, Adina L
AU  - Milac AL
FAU - Vieira, Wilfred D
AU  - Vieira WD
FAU - Yamaguchi, Yuji
AU  - Yamaguchi Y
FAU - Rouzaud, Francois
AU  - Rouzaud F
FAU - Petrescu, Andrei-J
AU  - Petrescu AJ
FAU - Lamoreux, M Lynn
AU  - Lamoreux ML
FAU - Hearing, Vincent J
AU  - Hearing VJ
LA  - eng
GR  - WT_/Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Biochem J
JT  - The Biochemical journal
JID - 2984726R
RN  - 0 (Melanins)
RN  - 0 (pheomelanin)
RN  - 12627-86-0 (eumelanin)
RN  - EC 5.3.- (Intramolecular Oxidoreductases)
RN  - EC 5.3.3.12 (dopachrome isomerase)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Binding Sites
MH  - Cells, Cultured
MH  - Gene Expression Regulation, Enzymologic
MH  - Intramolecular Oxidoreductases/*genetics/*metabolism
MH  - Melanins/*biosynthesis
MH  - Melanocytes/cytology/*metabolism
MH  - Mice
MH  - Molecular Sequence Data
MH  - Protein Conformation
MH  - Protein Transport
MH  - Sequence Homology, Amino Acid
PMC - PMC1276922
EDAT- 2005/06/18 09:00
MHDA- 2006/01/27 09:00
PMCR- 2006/04/15
CRDT- 2005/06/18 09:00
PHST- 2005/06/18 09:00 [pubmed]
PHST- 2006/01/27 09:00 [medline]
PHST- 2005/06/18 09:00 [entrez]
PHST- 2006/04/15 00:00 [pmc-release]
AID - BJ20042070 [pii]
AID - bj3910249 [pii]
AID - 10.1042/BJ20042070 [doi]
PST - ppublish
SO  - Biochem J. 2005 Oct 15;391(Pt 2):249-59. doi: 10.1042/BJ20042070.