"\u0160kopov\u00E1, V\u00E1clava" . . . . "[BDC820972891]" . "11"^^ . . . "I, P(1M0520), P(GA301/07/0600), Z(MSM0021620806)" . "Kmoch, Stanislav" . "Biochemical and Structural Analysis of 14 Mutant ADSL Enzyme Complexes and Correlation to Phenotypic Heterogeneity of Adenylosuccinate Lyase Deficiency"@en . . "11110" . . . "4" . . . "5"^^ . . "Hn\u00EDzda, Ale\u0161" . "Zik\u00E1nov\u00E1, Marie" . . . "1059-7794" . . "Biochemical and Structural Analysis of 14 Mutant ADSL Enzyme Complexes and Correlation to Phenotypic Heterogeneity of Adenylosuccinate Lyase Deficiency" . "RIV/00216208:11110/10:7879!RIV11-GA0-11110___" . "5"^^ . . . "Adenylosuccinate lyase (ADSL) deficiency, an inborn error of purine metabolism, leads to accumulation of dephosphorylated ADSL substrates SAICA-riboside (SAICAr) and succinyladenosine (S-Ado) in body fluids and affects the patients\u00B4 nervous system. Severity of symptoms differs and correlates with diverse S-Ado/SAICAr concentrations\u00B4 ratio in cerebrospinal fluid. To identify biochemical and structural basis of the S-Ado/SAICAr ratio and phenotypic heterogeneity we expressed and characterized 19 ADSL mutant proteins corresponding to 16 clinically well characterized genotypes. We found that phenotypic severity correlates with residual enzymatic activities and structural stability of the corresponding mutant ADSL complex and does not result from genotype-specific disproportional catalytic activities toward one of the enzyme substrates. It suggests that S-Ado/SAICAr ratio value is probably not predictive of phenotype severity but rather it may be secondary to degree of patient\u2019s development and brain matur"@en . . . "Krijt, Jakub" . . . . . "adenylosuccinate lyase; ADSL deficiency; phenotype heterogeneity; de novo purine synthesis; purine nucleotide cycle; intersubunit complementation; purine nucleotide cycle; bacillus-subtilis; skeletal-muscle; succinyladenosine; gene; site"@en . . . . "Biochemical and Structural Analysis of 14 Mutant ADSL Enzyme Complexes and Correlation to Phenotypic Heterogeneity of Adenylosuccinate Lyase Deficiency"@en . "31" . "Biochemical and Structural Analysis of 14 Mutant ADSL Enzyme Complexes and Correlation to Phenotypic Heterogeneity of Adenylosuccinate Lyase Deficiency" . . "248826" . . "US - Spojen\u00E9 st\u00E1ty americk\u00E9" . . "Adenylosuccinate lyase (ADSL) deficiency, an inborn error of purine metabolism, leads to accumulation of dephosphorylated ADSL substrates SAICA-riboside (SAICAr) and succinyladenosine (S-Ado) in body fluids and affects the patients\u00B4 nervous system. Severity of symptoms differs and correlates with diverse S-Ado/SAICAr concentrations\u00B4 ratio in cerebrospinal fluid. To identify biochemical and structural basis of the S-Ado/SAICAr ratio and phenotypic heterogeneity we expressed and characterized 19 ADSL mutant proteins corresponding to 16 clinically well characterized genotypes. We found that phenotypic severity correlates with residual enzymatic activities and structural stability of the corresponding mutant ADSL complex and does not result from genotype-specific disproportional catalytic activities toward one of the enzyme substrates. It suggests that S-Ado/SAICAr ratio value is probably not predictive of phenotype severity but rather it may be secondary to degree of patient\u2019s development and brain matur" . . "Human Mutation" . . "RIV/00216208:11110/10:7879" . . "000276810600009" .