PMID- 25450182
OWN - NLM
STAT- MEDLINE
DCOM- 20150311
LR  - 20161126
IS  - 0006-3002 (Print)
IS  - 0006-3002 (Linking)
VI  - 1850
IP  - 2
DP  - 2015 Feb
TI  - Mechanism of dopachrome tautomerization into 5,6-dihydroxyindole-2-carboxylic 
      acid catalyzed by Cu(II) based on quantum chemical calculations.
PG  - 281-6
LID - S0304-4165(14)00360-2 [pii]
LID - 10.1016/j.bbagen.2014.10.024 [doi]
AB  - BACKGROUND: Tautomerization of dopachrome to 5,6-dihydroxyindole-2-carboxylic 
      acid (DHICA) is a biologically crucial reaction relevant to melanin synthesis, 
      cellular antioxidation, and cross-talk among epidermal cells. Since dopachrome 
      spontaneously converts into 5,6-dihydroxyindole (DHI) via decarboxylation without 
      any enzymes at physiologically usual pH, the mechanism of how tautomerization to 
      DHICA occurs in physiological system is a subject of intense debate. A previous 
      work has found that Cu(II) is an important factor to catalyze the tautomerization 
      of dopachrome to DHICA. However, the effect of Cu(II) on the tautomerization has 
      not been clarified at the atomic level. METHODS: We propose the reaction 
      mechanism of the tautomerization to DHICA by Cu(II) from density functional 
      theory-based calculation. RESULTS: We clarified that the activation barriers of 
      alpha-deprotonation, beta-deprotonation, and decarboxylation from dopachrome are 
      significantly reduced by coordination of Cu(II) to quinonoid oxygens 
      (5,6-oxygens) of dopachrome, with the lowest activation barrier of 
      beta-deprotonation among them. In contrast to our previous work, in which 
      beta-deprotonation and quinonoid protonation (O5/O6-protonation) were shown to be 
      important to form DHI, our results show that the Cu(II) coordination to quinonoid 
      oxygens inhibits the quinonoid protonation, leading to the preference of proton 
      rearrangement from beta-carbon to carboxylate group but not to the quinonoid 
      oxygens. CONCLUSION: Integrating these results, we conclude that dopachrome 
      tautomerization first proceeds via proton rearrangement from beta-carbon to 
      carboxylate group and subsequently undergoes alpha-deprotonation to form DHICA. 
      GENERAL SIGNIFICANCE: This study would provide the biochemical basis of DHICA 
      metabolism and the generalized view of dopachrome conversion which is important 
      to understand melanogenesis.
CI  - Copyright (c) 2014 Elsevier B.V. All rights reserved.
FAU - Kishida, Ryo
AU  - Kishida R
AD  - Department of Applied Physics, Osaka University, Suita, Osaka, Japan.
FAU - Saputro, Adhitya G
AU  - Saputro AG
AD  - Department of Applied Physics, Osaka University, Suita, Osaka, Japan.
FAU - Kasai, Hideaki
AU  - Kasai H
AD  - Department of Applied Physics, Osaka University, Suita, Osaka, Japan; Center for 
      Atomic and Molecular Technologies, Osaka University, Suita, Osaka, Japan. 
      Electronic address: kasai@dyn.ap.eng.osaka-u.ac.jp.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20141028
PL  - Netherlands
TA  - Biochim Biophys Acta
JT  - Biochimica et biophysica acta
JID - 0217513
RN  - 0 (Indolequinones)
RN  - 0 (Indoles)
RN  - 3571-34-4 (dopachrome)
RN  - 4790-08-3 (5,6-dihydroxy-2-indolylcarboxylic acid)
RN  - 789U1901C5 (Copper)
SB  - IM
MH  - Catalysis
MH  - Copper/*chemistry
MH  - Indolequinones/*chemistry
MH  - Indoles/*chemistry
MH  - *Models, Chemical
MH  - Quantum Theory
OTO - NOTNLM
OT  - Copper
OT  - DHICA
OT  - Density functional theory
OT  - Dopachrome
OT  - Eumelanin
OT  - Melanin
EDAT- 2014/12/03 06:00
MHDA- 2015/03/12 06:00
CRDT- 2014/12/03 06:00
PHST- 2014/08/03 00:00 [received]
PHST- 2014/10/18 00:00 [revised]
PHST- 2014/10/21 00:00 [accepted]
PHST- 2014/12/03 06:00 [entrez]
PHST- 2014/12/03 06:00 [pubmed]
PHST- 2015/03/12 06:00 [medline]
AID - S0304-4165(14)00360-2 [pii]
AID - 10.1016/j.bbagen.2014.10.024 [doi]
PST - ppublish
SO  - Biochim Biophys Acta. 2015 Feb;1850(2):281-6. doi: 10.1016/j.bbagen.2014.10.024. 
      Epub 2014 Oct 28.