Succinic semialdehyde dehydrogenase from the parasitic cattle tick Rhipicephalus microplus: gene identification, biochemical characterization and comparison with the mouse ortholog.
The gamma-aminobutyric acid (GABA) degradation pathway consists of the enzymes GABA transaminase and succinic semialdehyde dehydrogenase (SSADH) and is essential for the development and functionality of the nervous system in mammals, while little is known on its role in invertebrates. In this study we report the gene identification, cDNA cloning and heterologous functional expression of a SSADH from the cattle tick Rhipicephalus (R.) microplus. In contrast to mammals and the insect model organism Drosophila melanogaster, which have one SSADH gene, R. microplus possesses several gene copies. One representative of these genes has been functionally expressed in Escherichia coli. This recombinant cattle tick protein has potent NAD(+)-dependent SSADH activity, but possesses also marked enzymatic activity on other aliphatic and aromatic aldehyde substrates. Comparison of R. microplus SSADH enzyme kinetic properties as well as substrate and inhibitor specificities with those of a recombinant mammalian SSADH reveals overall similarities, but also subtle differences, that may be exploited for the design of specific inhibitors with selective acaricidal activity.
Rothacker
Boris
B
Intervet Innovation GmbH, Zur Propstei, 55270 Schwabenheim, Germany.
Werr
Margaret
M
Ilg
Thomas
T
D000447:Aldehydes / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004926:Escherichia coli / Q000235:genetics; D018628:Gene Dosage; D015870:Gene Expression; D007700:Kinetics; D008969:Molecular Sequence Data; D009243:NAD / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D048494:Rhipicephalus / Q000201:enzymology* / Q000235:genetics; D016415:Sequence Alignment; D013379:Substrate Specificity; D050644:Succinate-Semialdehyde Dehydrogenase / Q000235:genetics* / Q000378:metabolism*
D000447:Aldehydes; D018076:DNA, Complementary; D004791:Enzyme Inhibitors; D011994:Recombinant Proteins; D009243:NAD; D050644:Succinate-Semialdehyde Dehydrogenase