Biochemical and Structural Analysis of 14 Mutant ADSL Enzyme Complexes and Correlation to Phenotypic Heterogeneity of Adenylosuccinate Lyase Deficiency

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11110%2F10%3A7879" target="_blank" >RIV/00216208:11110/10:7879 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00064165:_____/10:7879

Výsledek na webu

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DOI - Digital Object Identifier

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Jazyk výsledku

angličtina

Název v původním jazyce

Biochemical and Structural Analysis of 14 Mutant ADSL Enzyme Complexes and Correlation to Phenotypic Heterogeneity of Adenylosuccinate Lyase Deficiency

Popis výsledku v původním jazyce

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´ nervous system. Severity of symptoms differs and correlates with diverse S-Ado/SAICAr concentrations´ 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?s development

Název v anglickém jazyce

Biochemical and Structural Analysis of 14 Mutant ADSL Enzyme Complexes and Correlation to Phenotypic Heterogeneity of Adenylosuccinate Lyase Deficiency

Popis výsledku anglicky

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´ nervous system. Severity of symptoms differs and correlates with diverse S-Ado/SAICAr concentrations´ 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?s development

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

EB - Genetika a molekulární biologie

OECD FORD obor

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Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>Z - Vyzkumny zamer (s odkazem do CEZ)

Rok uplatnění

2010

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Human Mutation

ISSN

1059-7794

e-ISSN

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Svazek periodika

31

Číslo periodika v rámci svazku

4

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

11

Strana od-do

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Kód UT WoS článku

000276810600009

EID výsledku v databázi Scopus

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