A glycine-to-glutamate substitution abolishes alanine:glyoxylate aminotransferase catalytic activity in a subset of patients with primary hyperoxaluria type 1.
作者： P.Edward Purdue , Michael J. Lumb , Jennifer Allsop , Yohsuke Minatogawa , Christopher J. Danpure
DOI: 10.1016/0888-7543(92)90225-H
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摘要: Abstract We have synthesized and sequenced alanine:glyoxylate aminotransferase (AGT; HGMW-approved symbol for the gene—AGXT) cDNA from liver of a primary hyperoxaluria type 1 (PH1) patient who had normal levels hepatic peroxisomal immunoreactive AGT protein, but no catalytic activity. This revealed presence single point mutation (G → A at nucleotide 367), which is predicted to cause glycine-to-glutamate substitution residue 82 protein. located in exon 2 gene leads loss an AvaI restriction site. Exon 2-specific PCR followed by digestion showed that this was homozygous mutation. In addition, three other PH1 patients, one related two unrelated to, with enzymological phenotype similar first patient, were also shown be However, phenotypically lack The mechanism causes activity remains resolved. protein sequence region highly conserved between different mammals, significant local structural alterations.
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