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| http://purl.uniprot.org/citations/28866054 | http://www.w3.org/2000/01/rdf-schema#comment | "Substitutions within the cardenolide target site of several insects' Na,K-ATPase α-subunits may confer resistance against toxic cardenolides. However, to which extent these substitutions alter the Na,K-ATPase's kinetic properties and how they interact with different β-subunits is not clear. The cardenolide-adapted milkweed bug Oncopeltus fasciatus possesses three paralogs of the α-subunit (A, B, and C) that differ in number and identity of resistance-conferring substitutions. We introduced these substitutions into the α-subunit of Drosophila melanogaster and combined them with the β-subunits Nrv2.2 and Nrv3. The substitutions Q111T-N122H-F786N-T797A (A-copy mimic) and Q111T-N122H-F786N (B-copy mimic) mediated high insensitivity to ouabain, yet they drastically lowered ATPase activity. Remarkably, the identity of the β-subunit was decisive and all α-subunits were less active when combined with Nrv3 than when combined with Nrv2.2. Both the substitutions and the co-expressed β-subunit strongly affected the enyzme's affinity for Na+ and K+. Na+ affinity was considerably higher for all enzymes expressed with nrv3 while expression with nrv2.2 mostly increased K+ affinity. Our results provide the first evidence that resistance against cardenolides comes at the cost of significantly altered kinetic properties of the Na,K-ATPase. The β-subunit can strongly modulate these properties but cannot fully compensate for the effect of the substitutions."xsd:string |
| http://purl.uniprot.org/citations/28866054 | http://purl.org/dc/terms/identifier | "doi:10.1016/j.ibmb.2017.08.005"xsd:string |
| http://purl.uniprot.org/citations/28866054 | http://purl.uniprot.org/core/author | "Baum M."xsd:string |
| http://purl.uniprot.org/citations/28866054 | http://purl.uniprot.org/core/author | "Dobler S."xsd:string |
| http://purl.uniprot.org/citations/28866054 | http://purl.uniprot.org/core/author | "Dalla S."xsd:string |
| http://purl.uniprot.org/citations/28866054 | http://purl.uniprot.org/core/date | "2017"xsd:gYear |
| http://purl.uniprot.org/citations/28866054 | http://purl.uniprot.org/core/name | "Insect Biochem Mol Biol"xsd:string |
| http://purl.uniprot.org/citations/28866054 | http://purl.uniprot.org/core/pages | "43-50"xsd:string |
| http://purl.uniprot.org/citations/28866054 | http://purl.uniprot.org/core/title | "Substitutions in the cardenolide binding site and interaction of subunits affect kinetics besides cardenolide sensitivity of insect Na,K-ATPase."xsd:string |
| http://purl.uniprot.org/citations/28866054 | http://purl.uniprot.org/core/volume | "89"xsd:string |
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