1jpi

Phe232Leu mutant of human UROD, human uroporphyrinogen III decarboxylase

spinqualitylabelsall models 1jpi, resolution 2.30Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 1jpi is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.3Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease DCUP_HUMAN Defects in UROD are the cause of familial porphyria cutanea tarda (FPCT) [MIM:176100; also known as porphyria cutanea tarda type II. FPCT is an autosomal dominant disorder characterized by light-sensitive dermatitis, with onset in later life. It is associated with the excretion of large amounts of uroporphyrin in the urine. Iron overload is often present in association with varying degrees of liver damage. Besides the familial form of PCT, a relatively common idiosyncratic form is known in which only the liver enzyme is reduced. This form is referred to as porphyria cutanea tarda "sporadic" type or type I [MIM:176090. PCT type I occurs sporadically as an unusual accompaniment of common hepatic disorders such as alcohol-associated liver disease. Defects in UROD are the cause of hepatoerythropoietic porphyria (HEP) [MIM:176100. HEP is a rare autosomal recessive disorder. It is the severe form of cutaneous porphyria, and presents in infancy. The level of UROD is very low in erythrocytes and cultured skin fibroblasts, suggesting that HEP is the homozygous state for porphyria cutanea tarda. Function DCUP_HUMAN Catalyzes the decarboxylation of four acetate groups of uroporphyrinogen-III to yield coproporphyrinogen-III. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed Functional consequences of 12 mutations-10 missense, 1 splicing defect, and 1 frameshift mutation-were characterized in the uroporphyrinogen decarboxylase (URO-D) gene found in Utah pedigrees with familial porphyria cutanea tarda (F-PCT). All but one mutation altered a restriction site in the URO-D gene, permitting identification of affected relatives using a combination of polymerase chain reaction and restriction enzyme digestion. In a bacterial expression system, 3 of the missense mutants were found in inclusion bodies, but 7 were expressed as soluble proteins. Enzymatic activity of soluble, recombinant mutant URO-D genes ranged from 29% to 94% of normal. URO-D mRNA levels in Epstein-Barr-virus transformed cells derived from patients were normal (with the exception of the frameshift mutation) even though protein levels were lower than normal, suggesting that missense mutations generally cause unstable URO-Ds in vivo. The crystal structures of 3 mutant URO-Ds were solved, and the structural consequences of the mutations were defined. All missense mutations reported here and by others were mapped to the crystal structure of URO-D, and structural effects were predicted. These studies define structural and functional consequences of URO-D mutations occurring in patients with F-PCT. Functional consequences of naturally occurring mutations in human uroporphyrinogen decarboxylase.,Phillips JD, Parker TL, Schubert HL, Whitby FG, Hill CP, Kushner JP Blood. 2001 Dec 1;98(12):3179-85. PMID:11719352 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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