Biochemical and molecular genetic correlation in adenylosuccinate lyase deficiency.
An homology model of human adenylosuccinate lyase structure shows that P100A substitution distorts the amino acid chain of domain I in the proximity of His-86, which behaves as general acid in the catalysis, and may expose Cys-98 and Cys-99 to oxidising agents. This model is in line with the observation that the defective protein is strongly inhibited by 4-hydroxy-2-nonenal, an hydroxyalkenal that is known to form thio-ether linkage with proteins.
Salerno
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Department of Gynecology, Perinatology and Child Health, University of Roma La Sapienza, Roma, Italy.
Crifò
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D000264:Adenylosuccinate Lyase / Q000172:deficiency* / Q000235:genetics*; D000447:Aldehydes / Q000494:pharmacology; D001665:Binding Sites; D002384:Catalysis; D018360:Crystallography, X-Ray; D003545:Cysteine / Q000737:chemistry; D004220:Disulfides / Q000737:chemistry; D006801:Humans; D007700:Kinetics; D018384:Oxidative Stress; D017434:Protein Structure, Tertiary
D000447:Aldehydes; D004220:Disulfides; D000264:Adenylosuccinate Lyase; C027576:4-hydroxy-2-nonenal; D003545:Cysteine