1-L-methyltryptophan is a more effective inhibitor of vertebrate IDO2 enzymes than 1-D-methyltryptophan.
1-D-methyltryptophan (D-1MT) is an effective anti-cancer agent in mouse tumour models. It has been suggested to be a selective inhibitor of the recently described tryptophan-degrading enzyme indoleamine 2,3-dioxygenase 2 (IDO2) rather than the closely related enzyme IDO1. We found that mammalian (mouse, opossum and platypus), chicken, frog, and fish IDO2 could be functional tryptophan-catabolising enzymes. The characteristics of pH-dependent activity and inhibitor selectivity were conserved amongst the vertebrate IDO2 proteins tested. Like IDO1 enzymes, the enzymatic activity of all IDO2s was inhibited by L-1MT but not by D-1MT in a cell-free assay. When IDO2s were expressed in mammalian cells, L-1MT was also a better inhibitor than D-1MT.
Yuasa
Hajime J
HJ
Laboratory of Biochemistry, Department of Applied Science, Faculty of Science, National University Corporation Kochi University, Kochi 780-8520, Japan. julie@kochi-u.ac.jp
Ball
Helen J
HJ
Austin
Christopher J D
CJ
Hunt
Nicholas H
NH
D000818:Animals; D001001:Anura; D002645:Chickens; D003001:Cloning, Molecular; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D005399:Fishes; D006801:Humans; D006863:Hydrogen-Ion Concentration; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D007700:Kinetics; D051379:Mice; D013237:Stereoisomerism; D013379:Substrate Specificity; D014364:Tryptophan / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology
D004791:Enzyme Inhibitors; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; C028129:tryptophan methyl ester; D014364:Tryptophan