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• W2357802092 endingPage "1890" @default.
• W2357802092 startingPage "1883" @default.
• W2357802092 abstract "Thiamin plays a critical role in cellular energy metabolism. Mammalian cells obtain the vitamin from their surroundings, converted it to thiamin pyrophosphate (TPP) in the cytoplasm, followed by uptake of TPP by mitochondria via a carrier-mediated process that involves the MTPPT (product of the SLC25A19 gene). Previous studies have characterized different physiological/biological aspects of the human MTPPT (hMTPPT), but less is known about structural features that are important for its function. Here, we used a protein-docking model (“Phyre2” and “DockingServer”) to predict residues that may be important for function (substrate recognition) of the hMTPPT; we also examined the role of conserved positively-charged residues predicted (“PRALINE”) to be in the trans-membrane domains (TMDs) in uptake of the negatively-charged TPP. Among the six residues predicted by the docking model (i.e., Thr29, Arg30, Ile33, Ser34, Asp37 and Phe298), only Ile33, Ser34 and Asp37 were found to be critical for function. While no change in translational efficiency/protein stability of the Ser34 mutant was observed, both the Ile33 and Asp37 mutants showed a decrease in this parameter(s); there was also a decrease in the expression of the latter two mutants in mitochondria. A need for a polar residue at position 34 of the hMTPPT was evident. Our findings with the positively-charged residues (i.e., His82, His137, Lys231 and Lys291) predicted in the TMD showed that His137 and Lys291 are important for function (via a role in proper delivery of the protein to mitochondria). These investigations provide important information about the structure-function relationship of the hMTPPT." @default.
• W2357802092 created "2016-06-24" @default.
• W2357802092 creator A5039622853 @default.
• W2357802092 creator A5060327315 @default.
• W2357802092 creator A5062861469 @default.
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• W2357802092 date "2016-08-01" @default.
• W2357802092 modified "2023-10-17" @default.
• W2357802092 title "Structure-function characterization of the human mitochondrial thiamin pyrophosphate transporter (hMTPPT; SLC25A19 ): Important roles for Ile 33 , Ser 34 , Asp 37 , His 137 and Lys 291" @default.
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• W2357802092 doi "https://doi.org/10.1016/j.bbamem.2016.05.011" @default.
• W2357802092 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4900926" @default.
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• W2357802092 hasPublicationYear "2016" @default.
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