Functional characterization of two variant human GSTO 1-1s (Ala140Asp and Thr217Asn).
Glutathione-S-transferase class Omega (GSTO 1-1) belongs to a new subfamily of GSTs, which is identical with human monomethylarsonic acid (MMA(V)) reductase, the rate limiting enzyme for biotransformation of inorganic arsenic, environmental carcinogen. Recombinant GSTO 1-1 variants (Ala140Asp and Thr217Asn) were functionally characterized using representative substrates. No significant difference was observed in GST activity towards 1-chloro-2,4-dinitrobenzene, whereas thioltransferase activity was decreased to 75% (Ala140Asp) and 40% (Thr217Asn) of the wild-type GSTO 1-1. For MMA(V) reductase activity, the Ala140Asp variant exhibited similar kinetics to wild type, while the Thr217Asn variant had lower V(max) (56%) and K(m) (64%) values than the wild-type enzyme. The different activities of the enzyme variants may influence both the intracellular thiol status and arsenic biotransformation. This can help explain the variation between individuals in their susceptibility to oxidative stress and inorganic arsenic.
Tanaka-Kagawa
Toshiko
T
Division of Environmental Chemistry, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan.
Jinno
Hideto
H
Hasegawa
Tatsuya
T
Makino
Yuko
Y
Seko
Yoshiyuki
Y
Hanioka
Nobumitsu
N
Ando
Masanori
M
D001152:Arsenicals / Q000378:metabolism; D001665:Binding Sites; D004137:Dinitrochlorobenzene / Q000378:metabolism; D004220:Disulfides / Q000378:metabolism; D005982:Glutathione Transferase / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D007509:Irritants / Q000378:metabolism; D007527:Isoenzymes / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D008958:Models, Molecular; D015394:Molecular Structure; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D013723:Teratogens / Q000378:metabolism
D001152:Arsenicals; D004137:Dinitrochlorobenzene; D004220:Disulfides; D007509:Irritants; D007527:Isoenzymes; D011993:Recombinant Fusion Proteins; D013723:Teratogens; D005982:Glutathione Transferase; C020300:monomethylarsonic acid