PMID- 24875753
OWN - NLM
STAT- MEDLINE
DCOM- 20150828
LR  - 20211108
IS  - 1438-2199 (Electronic)
IS  - 0939-4451 (Linking)
VI  - 46
IP  - 9
DP  - 2014 Sep
TI  - Human indoleamine 2,3-dioxygenase-2 has substrate specificity and inhibition 
      characteristics distinct from those of indoleamine 2,3-dioxygenase-1.
PG  - 2155-63
LID - 10.1007/s00726-014-1766-3 [doi]
AB  - Indoleamine 2,3-dioxygenase-2 (IDO2) is one of three enzymes (alongside 
      tryptophan 2,3-dioxygenase and indoleamine 2,3-dioxygenase (IDO1)) that catalyse 
      dioxygenation of L-tryptophan as the first step in the kynurenine pathway. 
      Despite the reported expression of IDO2 in tumours, some fundamental 
      characteristics of the enzyme, such as substrate specificity and inhibition 
      selectivity, are still to be clearly defined. In this study, we report the 
      kinetic and inhibition characteristics of recombinant human IDO2. Choosing from a 
      series of likely IDO2 substrates, we screened 54 tryptophan derivatives and 
      tryptophan-like molecules, and characterised the 8 with which the enzyme was most 
      active. Specificity of IDO2 for the two isomers of 1-methyltryptophan was also 
      evaluated and the findings compared with those obtained in other studies on IDO2 
      and IDO1. Interestingly, IDO2 demonstrates behaviour distinct from that of IDO1 
      in terms of substrate specificity and affinity, such that we have identified 
      tryptophan derivatives that are mutually exclusive as substrates for IDO1 and 
      IDO2. Our results support the idea that the antitumour activity of 1-Me-D-Trp is 
      unlikely to be related with competitive inhibition of IDO2, and also imply that 
      there are subtle differences in active site structure in the two enzymes that may 
      be exploited in the development of specific inhibitors of these enzymes, a route 
      which may prove important in defining their role(s) in cancer.
FAU - Pantouris, Georgios
AU  - Pantouris G
AD  - EaStCHEM, School of Chemistry, University of Edinburgh, West Mains Road, 
      Edinburgh, EH9 3JJ, UK.
FAU - Serys, Martynas
AU  - Serys M
FAU - Yuasa, Hajime J
AU  - Yuasa HJ
FAU - Ball, Helen J
AU  - Ball HJ
FAU - Mowat, Christopher G
AU  - Mowat CG
LA  - eng
PT  - Journal Article
DEP - 20140530
PL  - Austria
TA  - Amino Acids
JT  - Amino acids
JID - 9200312
RN  - 0 (IDO1 protein, human)
RN  - 0 (IDO2 protein, human)
RN  - 0 (Indoleamine-Pyrrole 2,3,-Dioxygenase)
RN  - 0 (Recombinant Proteins)
RN  - 7303-49-3 (tryptophan methyl ester)
RN  - 8DUH1N11BX (Tryptophan)
SB  - IM
MH  - Humans
MH  - Indoleamine-Pyrrole 2,3,-Dioxygenase/antagonists & inhibitors/*chemistry/genetics
MH  - Recombinant Proteins/chemistry/genetics
MH  - Substrate Specificity/physiology
MH  - Tryptophan/*analogs & derivatives/chemistry
EDAT- 2014/05/31 06:00
MHDA- 2015/09/01 06:00
CRDT- 2014/05/31 06:00
PHST- 2013/11/07 00:00 [received]
PHST- 2014/05/14 00:00 [accepted]
PHST- 2014/05/31 06:00 [entrez]
PHST- 2014/05/31 06:00 [pubmed]
PHST- 2015/09/01 06:00 [medline]
AID - 10.1007/s00726-014-1766-3 [doi]
PST - ppublish
SO  - Amino Acids. 2014 Sep;46(9):2155-63. doi: 10.1007/s00726-014-1766-3. Epub 2014 
      May 30.