A member of the aldoketo reductase family confers methotrexate resistance in Leishmania.
作者： H.L. Callahan , S.M. Beverley
DOI: 10.1016/S0021-9258(18)35743-0
关键词:
摘要: Methotrexate (MTX)-resistant mutants of the parasitic protozoan Leishmania have been used as models for mechanism and genetic basis drug resistance in trypanosomatids other cells. Three mechanisms to MTX, a dihydrofolate reductase inhibitor, described Leishmania: decreased uptake accumulation MTX via folate/MTX transporter, amplification overexpression reductase-thymidylate synthase gene, extrachromosomal H region DNA. We now identified hmtxr gene conferring using transfection-based approach. Data base searches show that predicted HMTXr protein is related members polyol dehydrogenase/carbonyl family aldoketo reductases, whose substrates include polyols, quinones, steroids, prostaglandins, fatty acids, pterins. therefore propose also an oxidoreductase suggest several biochemical could be exploited design parasite-specific inhibitors.
sci-hub.st 参考文章(39)
H Yamamoto-Otake, Y Koyama, T Horiuchi, E Nakano, Cloning, sequencing, and expression of the N-acyl-D-mannosamine dehydrogenase gene from Flavobacterium sp. strain 141-8 in Escherichia coli. Applied and Environmental Microbiology. ,vol. 57, pp. 1418- 1422 ,(1991) , 10.1128/AEM.57.5.1418-1422.1991
K Kaur, T Coons, K Emmett, B Ullman, Methotrexate-resistant Leishmania donovani genetically deficient in the folate-methotrexate transporter. Journal of Biological Chemistry. ,vol. 263, pp. 7020- 7028 ,(1988) , 10.1016/S0021-9258(18)68598-9
H.L. Callahan, S.M. Beverley, Heavy metal resistance: a new role for P-glycoproteins in Leishmania. Journal of Biological Chemistry. ,vol. 266, pp. 18427- 18430 ,(1991) , 10.1016/S0021-9258(18)55077-8
Michael E. Baker, A common ancestor for human placental 17β‐hydroxysteroid dehydrogenase,
Streptomyces coelicolor
actIII protein, and
Drosophila melanogaster
alcohol dehydrogenase The FASEB Journal. ,vol. 4, pp. 222- 226 ,(1990) , 10.1096/FASEBJ.4.2.2153594
B Wermuth, K M Bohren, G Heinemann, J P von Wartburg, K H Gabbay, Human carbonyl reductase. Nucleotide sequence analysis of a cDNA and amino acid sequence of the encoded protein Journal of Biological Chemistry. ,vol. 263, pp. 16185- 16188 ,(1988) , 10.1016/S0021-9258(18)37576-8
Hiroshi Ichinose, Setsuko Katoh, Terumi Sueoka, Koiti Titani, Keisuke Fujita, Toshiharu Nagatsu, Cloning and sequencing of cDNA encoding human sepiapterin reductase: An enzyme involved in tetrahydrobiopterin biosynthesis Biochemical and Biophysical Research Communications. ,vol. 179, pp. 183- 189 ,(1991) , 10.1016/0006-291X(91)91352-D
M. Ouellette, F. Fase-Fowler, P. Borst, The amplified H circle of methotrexate-resistant leishmania tarentolae contains a novel P-glycoprotein gene. The EMBO Journal. ,vol. 9, pp. 1027- 1033 ,(1990) , 10.1002/J.1460-2075.1990.TB08206.X
G M Kapler, C M Coburn, S M Beverley, Stable transfection of the human parasite Leishmania major delineates a 30-kilobase region sufficient for extrachromosomal replication and expression. Molecular and Cellular Biology. ,vol. 10, pp. 1084- 1094 ,(1990) , 10.1128/MCB.10.3.1084
Maria Krook, L. Marekov, Hans Jörnvall, Purification and structural characterization of placental NAD(+)-linked 15-hydroxyprostaglandin dehydrogenase. The primary structure reveals the enzyme to belong to the short-chain alcohol dehydrogenase family. Biochemistry. ,vol. 29, pp. 738- 743 ,(1990) , 10.1021/BI00455A021
Charles Mark Ensor, Hsin-Hsiung Tai, Site-directed mutagenesis of the conserved tyrosine 151 of human placental NAD+-dependent 15-hydroxyprostaglandin dehydrogenase yields a catalytically inactive enzyme Biochemical and Biophysical Research Communications. ,vol. 176, pp. 840- 845 ,(1991) , 10.1016/S0006-291X(05)80262-1