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Structural and kinetic characterization of mutant human uroporphyrinogen decarboxylases
Corresponding Author(s) : C A Warby
Cellular and Molecular Biology,
Vol. 55 No. 2: Porphyrias and associated pathologies. Biochemistry and molecular biology Part 2
Abstract
Porphyria cutanea tarda (PCT) is caused by inhibition of uroporphyrinogen decarboxylase (URO-D) activity in hepatocytes. Subnormal URO-D activity results in accumulation and urinary excretion of uroporphyrin and heptacarboxyl porphyrin. Heterozygosity for mutations in the URO-D gene is found in the familial form of PCT (F-PCT). Over 70 mutations of URO-D have been described but very few have been characterized structurally. Here we characterize 3 mutations in the URO-D gene found in patients with F-PCT, G318R, K297N, and D306Y. Expression of the D306Y mutation results in an insoluble recombinant protein. G318R and K297N have little effect on the structure or activity of recombinant URO-D, but the proteins display reduced stability in vitro.
Keywords
Porphyria cutanea tarda
uroporphyrinogen decarboxylase.
Warby, C. A., Phillips, J. D., Bergonia, H. A., Whitby, F. G., Hill, C. P., & Kushner, J. P. (2009). Structural and kinetic characterization of mutant human uroporphyrinogen decarboxylases. Cellular and Molecular Biology, 55(2), 40–45. Retrieved from http://mail.cellmolbiol.org/index.php/CMB/article/view/1086
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