The overlapping 6 fragments of the HMBS gene, amplified by the reverse transcript-polymerase chain reaction, were analyzed by the single-strand conformation polymorphism with silver staining technique. We studied the gene mutation in two unrelated AIP families in the San-in district, a local area of Western Japan.
The hydroxymethylbilane synthase ( HMBS) mRNAs from 44 control individuals and 30 patients suffering from acute intermittent porphyria (AIP), were screened for length differences by reverse transcriptase polymerase chain reaction ( RT-PCR) and any abnormalities were characterized by direct sequencing.Reporter gene and electrophoretic mobility shift assays show that the G nucleotide at position -154, the most 5' of several transcription-initiation sites in the ubiquitous HMBS promoter, which lies immediately 3' to a transcription-factor IIB binding motif, is essential for normal transcription.Novel mutation and polymorphisms of the HMBS gene detected by denaturing HPLC.Several crystallographic structures of HMBS have been previously determined, most recently including by time-resolved Laue protein crystallography of the Lys59Gln mutant form with reaction initiation undertaken by use of a flow cell carrying the substrate PBG.Īnalytical, diagnostic and therapeutic context of HMBS The accumulation of protein deposits in neurons, in vitro proteasome assays and over-expression studies suggest that impairment of the ubiquitin-proteasome system (UPS) may be a common mechanism of pathogenesis in polyglutamine diseases such as Huntington disease and spinocerebellar ataxias (SCAs).An inherited deficiency of porphobilinogen deaminase in humans is responsible for the autosomal dominant disease acute intermittent porphyria.Porphobilinogen deaminase mutants that cause acute intermittent porphyria have been investigated as recombinant proteins expressed in Escherichia coli, yielding important insight into the mechanism of dipyrromethane cofactor assembly and tetrapyrrole chain polymerization.The role of conserved arginine residues in hydroxymethylbilane synthase was investigated by replacing these residues in the enzyme from Escherichia coli with leucine residues by using site-directed mutagenesis.Acute intermittent porphyria caused by an arginine to histidine substitution (R26H) in the cofactor-binding cleft of porphobilinogen deaminase.Chemical compound and disease context of HMBS
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