Mouse and human indoleamine 2,3-dioxygenase display some distinct biochemical and structural properties.
The hemoprotein indoleamine 2,3-dioxygenase (IDO) is the first and rate-limiting enzyme in the most significant pathway for mammalian tryptophan metabolism. It has received considerable attention in recent years, particularly due to its dual role in immunity and the pathogenesis of many diseases. Reported here are differences and similarities between biochemical behaviour and structural features of recombinant human IDO and recombinant mouse IDO. Significant differences were observed in the conversion of substrates and pH stability. Differences in inhibitor potency and thermal stability were also noted. Secondary structural features were broadly similar but variation between species was apparent, particularly in the alpha-helix portion of the enzymes. With mouse models substituting for human diseases, the differences between mouse and human IDO must be recognised before applying experimental findings from one system to the next.
Austin
Christopher J D
CJ
Molecular Immunopathology Unit, Bosch Institute, University of Sydney, Sydney, Australia. caustin@mail.med.usyd.edu.au
Astelbauer
Florian
F
Kosim-Satyaputra
Priambudi
P
Ball
Helen J
HJ
Willows
Robert D
RD
Jamie
Joanne F
JF
Hunt
Nicholas H
NH
D000595:Amino Acid Sequence; D000818:Animals; D002942:Circular Dichroism; D004795:Enzyme Stability; D006801:Humans; D006863:Hydrogen-Ion Concentration; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000737:chemistry* / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D007700:Kinetics; D007737:Kynurenine / Q000737:chemistry / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D017510:Protein Folding; D017433:Protein Structure, Secondary; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D016415:Sequence Alignment; D013696:Temperature
D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D011994:Recombinant Proteins; D007737:Kynurenine