PMID- 1859367
OWN - NLM
STAT- MEDLINE
DCOM- 19910827
LR  - 20190501
IS  - 0264-6021 (Print)
IS  - 1470-8728 (Electronic)
IS  - 0264-6021 (Linking)
VI  - 277 ( Pt 2)
IP  - Pt 2
DP  - 1991 Jul 15
TI  - Specificity of dopachrome tautomerase and inhibition by carboxylated indoles. 
      Considerations on the enzyme active site.
PG  - 393-7
AB  - Dopachrome tautomerase (EC 5.3.2.3) catalyses the tautomerization of dopachrome 
      to 5,6-dihydroxyindole-2-carboxylic acid (DHICA) within the melanin-formation 
      pathway. We have analysed a series of substrate analogues and related compounds 
      as possible substrates and inhibitors of tautomerization. The enzyme appears to 
      be highly specific since D-dopachrome, alpha-methyldopachrome, dopaminochrome, 
      adrenochrome methyl ether and deoxyadrenochrome are not substrates. Conversely, 
      dopachrome tautomerase catalyses the tautomerization of dopachrome methyl ester, 
      suggesting that a carboxy group, either free or as a methyl ester, is essential 
      for enzyme recognition. No inhibition of dopachrome tautomerization was observed 
      in the presence of either semiquinonic compounds, such as tropolone and 
      L-mimosine, or pyrrole-2-carboxylic acid and unsubstituted indole. However, a 
      number of indole derivatives, including DHICA, the product of dopachrome 
      tautomerization, and the analogues 5-hydroxyindole-2-carboxylic and 
      indole-2-carboxylic acid were able to inhibit the enzyme. Furthermore, indoles 
      with a side chain at position 3 of the ring and containing a carboxylic group at 
      the gamma-position of this chain, such as L-tryptophan or indole-3-propionic 
      acid, are stronger inhibitors of the enzyme. Indole-3-carboxylic acid, 
      indole-3-acetic acid and indole-3-butyric acid are very weak inhibitors, showing 
      that the carboxylic group needs to be located at an optimal distance from the 
      indole ring to mimic the carboxylic group at position 2 on the authentic 
      substrate.
FAU - Aroca, P
AU  - Aroca P
AD  - Departmento Bioquimica y Biologia Molecular, Facultad de Medicina, Universidad de 
      Murcia, Spain.
FAU - Solano, F
AU  - Solano F
FAU - Garcia-Borron, J C
AU  - Garcia-Borron JC
FAU - Lozano, J A
AU  - Lozano JA
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Biochem J
JT  - The Biochemical journal
JID - 2984726R
RN  - 0 (Carboxylic Acids)
RN  - 0 (Indoles)
RN  - EC 5.- (Isomerases)
RN  - EC 5.3.- (Intramolecular Oxidoreductases)
RN  - EC 5.3.3.12 (dopachrome isomerase)
RN  - SU46BAM238 (Ammonium Sulfate)
SB  - IM
MH  - Ammonium Sulfate
MH  - Animals
MH  - Carboxylic Acids/*pharmacology
MH  - Cell Line
MH  - Female
MH  - Indoles/*pharmacology
MH  - *Intramolecular Oxidoreductases
MH  - Isomerases/antagonists & inhibitors/isolation & purification/*metabolism
MH  - Kinetics
MH  - Male
MH  - Melanoma, Experimental/*enzymology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Inbred DBA
MH  - Structure-Activity Relationship
MH  - Substrate Specificity
PMC - PMC1151246
EDAT- 1991/07/15 00:00
MHDA- 1991/07/15 00:01
PMCR- 1991/07/15
CRDT- 1991/07/15 00:00
PHST- 1991/07/15 00:00 [pubmed]
PHST- 1991/07/15 00:01 [medline]
PHST- 1991/07/15 00:00 [entrez]
PHST- 1991/07/15 00:00 [pmc-release]
AID - 10.1042/bj2770393 [doi]
PST - ppublish
SO  - Biochem J. 1991 Jul 15;277 ( Pt 2)(Pt 2):393-7. doi: 10.1042/bj2770393.