Show simple item record

AuthorAl-Sadeq, Duaa W.
AuthorThanassoulas, Angelos
AuthorIslam, Zeyaul
AuthorKolatkar, Prasanna
AuthorAl-Dewik, Nader
AuthorSafieh-Garabedian, Bared
AuthorNasrallah, Gheyath K.
AuthorNomikos, Michail
Available date2022-04-24T08:28:09Z
Publication Date2022-07-01
Publication NameBiochimica et Biophysica Acta - General Subjects
Identifierhttp://dx.doi.org/10.1016/j.bbagen.2022.130148
CitationAl-Sadeq, D. W., Thanassoulas, A., Islam, Z., Kolatkar, P., Al-Dewik, N., Safieh-Garabedian, B., ... & Nomikos, M. (2022). Pyridoxine non-responsive R336C mutation alters the molecular properties of cystathionine beta-synthase leading to severe homocystinuria phenotype. Biochimica et Biophysica Acta (BBA)-General Subjects, 130148.
ISSN03044165
URIhttps://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85128216461&origin=inward
URIhttp://hdl.handle.net/10576/30247
AbstractThe prevalence of homocystinuria in Qatar is 1:1800, mainly due to a founder missense mutation p.R336C. • The cystathionine beta-synthase (CBS) R336C mutant was bacterially expressed, purified and its molecular properties were compared to CBS wild type (WT) recombinant protein. • Our data revealed that p.R336C mutation results in a dramatic reduction (∼86%) of CBS enzymatic activity. • Circular Dichroism experiments suggested that the p.R336C mutation does not significantly alter the secondary structure of the CBS protein. • CD spectra also revealed distinct differences in the thermal unfolding mechanisms of CBS WT and R336C mutant protein species. • Chemical denaturation experiments indicated that the WT CBS protein is thermodynamically more stable than the R336C mutant, suggesting a destabilizing effect of the p.R336C mutation. • This study provides mechanistic insight into the pathogenicity of the p.R336C mutation that leads to a severe homocystinuria phenotype.
SponsorThis publication was made possible by GSRA grant, GSRA6-1-0413-19013, from the Qatar National Research Fund (a member of Qatar Foundation). In addition, NA would like to thank fund from The Medical Research Center at Hamad Medical Corporation for IRGC-06-SI-19-167 grant. The statements made herein are solely the responsibility of the authors. Open Access funding provided by the Qatar National Library.
Languageen
PublisherElsevier
SubjectBiochemical characterization
Biophysical characterization
Cystathionine beta-synthase
Homocystinuria
R336C mutation
TitlePyridoxine non-responsive p.R336C mutation alters the molecular properties of cystathionine beta-synthase leading to severe homocystinuria phenotype
TypeArticle
Issue Number7
Volume Number1866
dc.accessType Open Access


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record