title: Structural and kinetic characterization of mutant human uroporphyrinogen decarboxylases.
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.
authors: Department of Medicine, University of Utah School of Medicine, Salt Lake City, Utah 84132, USA.
authors: C A
authors: CA
authors: Warby
authors: J D
authors: JD
authors: Phillips
authors: H A
authors: HA
authors: Bergonia
authors: F G
authors: FG
authors: Whitby
authors: C P
authors: CP
authors: Hill
authors: J P
authors: JP
authors: Kushner
mesh_terms: D000328:Adult; D000368:Aged; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D005260:Female; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D017119:Porphyria Cutanea Tarda / Q000209:etiology / Q000235:genetics; D055550:Protein Stability; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics; D014575:Uroporphyrinogen Decarboxylase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D011994:Recombinant Proteins; D014575:Uroporphyrinogen Decarboxylase