PMID- 20140689
OWN - NLM
STAT- MEDLINE
DCOM- 20101004
LR  - 20131121
IS  - 1438-2199 (Electronic)
IS  - 0939-4451 (Linking)
VI  - 39
IP  - 2
DP  - 2010 Jul
TI  - Biochemical characteristics and inhibitor selectivity of mouse indoleamine 
      2,3-dioxygenase-2.
PG  - 565-78
LID - 10.1007/s00726-010-0475-9 [doi]
AB  - The first step in the kynurenine pathway of tryptophan catabolism is the cleavage 
      of the 2,3-double bond of the indole ring of tryptophan. In mammals, this 
      reaction is performed independently by indoleamine 2,3-dioxygenase-1 (IDO1), 
      tryptophan 2,3-dioxygenase (TDO) and the recently discovered indoleamine 
      2,3-dioxygenase-2 (IDO2). Here we describe characteristics of a purified 
      recombinant mouse IDO2 enzyme, including its pH stability, thermal stability and 
      structural features. An improved assay system for future studies of 
      recombinant/isolated IDO2 has been developed using cytochrome b (5) as an 
      electron donor. This, the first description of the interaction between IDO2 and 
      cytochrome b (5), provides further evidence of the presence of a physiological 
      electron carrier necessary for activity of enzymes in the "IDO family". Using 
      this assay, the kinetic activity and substrate range of IDO2 were shown to be 
      different to those of IDO1. 1-Methyl-D-tryptophan, a current lead IDO inhibitor 
      used in clinical trials, was a poor inhibitor of both IDO1 and IDO2 activity. 
      This suggests that its immunosuppressive effect may be independent of 
      pharmacological inhibition of IDO enzymes, in the mouse at least. The different 
      biochemical characteristics of the mouse IDO proteins suggest that they have 
      evolved to have distinct biological roles.
FAU - Austin, Christopher Jonathan Daraius
AU  - Austin CJ
AD  - Molecular Immunopathology Unit, Discipline of Pathology and Bosch Institute, 
      University of Sydney, Camperdown, NSW, 2006, Australia.
FAU - Mailu, B M
AU  - Mailu BM
FAU - Maghzal, G J
AU  - Maghzal GJ
FAU - Sanchez-Perez, A
AU  - Sanchez-Perez A
FAU - Rahlfs, S
AU  - Rahlfs S
FAU - Zocher, K
AU  - Zocher K
FAU - Yuasa, H J
AU  - Yuasa HJ
FAU - Arthur, J W
AU  - Arthur JW
FAU - Becker, K
AU  - Becker K
FAU - Stocker, R
AU  - Stocker R
FAU - Hunt, N H
AU  - Hunt NH
FAU - Ball, H J
AU  - Ball HJ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100207
PL  - Austria
TA  - Amino Acids
JT  - Amino acids
JID - 9200312
RN  - 0 (Indoleamine-Pyrrole 2,3,-Dioxygenase)
RN  - 0 (Recombinant Proteins)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - 7303-49-3 (tryptophan methyl ester)
RN  - 8DUH1N11BX (Tryptophan)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Enzyme Stability
MH  - Humans
MH  - Hydrogen-Ion Concentration
MH  - Indoleamine-Pyrrole 2,3,-Dioxygenase/*antagonists & inhibitors/*metabolism
MH  - Kinetics
MH  - Mice
MH  - Models, Molecular
MH  - Molecular Sequence Data
MH  - Nitric Oxide/pharmacology
MH  - Recombinant Proteins/isolation & purification
MH  - Sequence Alignment
MH  - Tryptophan/analogs & derivatives/pharmacology
EDAT- 2010/02/09 06:00
MHDA- 2010/10/05 06:00
CRDT- 2010/02/09 06:00
PHST- 2009/08/24 00:00 [received]
PHST- 2010/01/06 00:00 [accepted]
PHST- 2010/02/09 06:00 [entrez]
PHST- 2010/02/09 06:00 [pubmed]
PHST- 2010/10/05 06:00 [medline]
AID - 10.1007/s00726-010-0475-9 [doi]
PST - ppublish
SO  - Amino Acids. 2010 Jul;39(2):565-78. doi: 10.1007/s00726-010-0475-9. Epub 2010 Feb 
      7.