Chaperone therapy for homocystinuria: the rescue of CBS mutations by heme arginate

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11110%2F15%3A10294808" target="_blank" >RIV/00216208:11110/15:10294808 - isvavai.cz</a>

Alternative codes found

RIV/00064165:_____/15:10294808

Result on the web

<a href="http://dx.doi.org/10.1007/s10545-014-9781-9" target="_blank" >http://dx.doi.org/10.1007/s10545-014-9781-9</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1007/s10545-014-9781-9" target="_blank" >10.1007/s10545-014-9781-9</a>

Result language

angličtina

Original language name

Chaperone therapy for homocystinuria: the rescue of CBS mutations by heme arginate

Original language description

Classical homocystinuria is caused by mutations in the cystathionine beta-synthase (CBS) gene. Previous experiments in bacterial and yeast cells showed that many mutant CBS enzymes misfold and that chemical chaperones enable proper folding of a number ofmutations. In the present study, we tested the extent of misfolding of 27 CBS mutations previously tested in E. coli under the more folding-permissive conditions of mammalian CHO-K1 cells and the ability of chaperones to rescue the conformation of thesemutations. Expression of mutations in mammalian cells increased the median activity 16-fold and the amount of tetramers 3.2-fold compared with expression in bacteria. Subsequently, we tested the responses of seven selected mutations to three compounds with chaperone-like activity. Aminooxyacetic acid and 4-phenylbutyric acid exhibited only a weak effect. In contrast, heme arginate substantially increased the formation of mutant CBS protein tetramers (up to sixfold) and rescued catalytic

Czech name

—

Czech description

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Type

J_x - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)

CEP classification

EB - Genetics and molecular biology

OECD FORD branch

—

Project

—

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2015

Confidentiality

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

Name of the periodical

Journal of Inherited Metabolic Disease

ISSN

0141-8955

e-ISSN

—

Volume of the periodical

38

Issue of the periodical within the volume

2

Country of publishing house

NL - THE KINGDOM OF THE NETHERLANDS

Number of pages

8

Pages from-to

287-294

UT code for WoS article

000350360200010

EID of the result in the Scopus database

2-s2.0-84925504823