Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:4.2.1.22 (
cystathionine beta-synthase
)
965
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
We determined the molecular basis of
cystathionine beta-synthase
(
CBS
) deficiency in a partially pyridoxine-responsive homocystinuria patient. Direct sequencing of the entire
CBS
cDNA revealed the presence of a homozygous G1330A transition. This mutation causes an amino acid change from
aspartic acid
to asparagine (D444N) in the regulatory domain of the protein and abolishes a TaqI restriction site at DNA level. Despite the homozygous mutation,
CBS
activities in extracts of cultured fibroblasts of this patient were not in the homozygous but in the heterozygous range. Furthermore, we observed no stimulation of
CBS
activity by S-adenosylmethionine, contrary to a threefold stimulation in control fibroblast extract. The mutation was introduced in an E. coli expression system and
CBS
activities were measured after addition of different S-adenosylmethionine concentrations (0-200 microM). Again, we observed a defective stimulation of
CBS
activity by S-adenosylmethionine in the mutated construct, whereas the normal construct showed a threefold stimulation in activity. These data suggest that this D444N mutation interferes in S-adenosylmethionine regulation of
CBS
. Furthermore, it indicates the importance of S-adenosylmethionine regulation of the transsulfuration pathway in homocysteine homeostasis in humans.
...
PMID:Defective cystathionine beta-synthase regulation by S-adenosylmethionine in a partially pyridoxine responsive homocystinuria patient. 875 36
