作者
DS Froese, S Healy, M McDonald, G Kochan, U Oppermann, FH Niesen, RA Gravel
发表日期
2010/5/31
期刊
Molecular genetics and metabolism
卷号
100
期号
1
页码范围
29-36
出版商
Academic Press
简介
Methylmalonic aciduria and homocystinuria, cblC type, is the most common inborn error of cellular vitamin B12 metabolism. We previously showed that the protein carrying the mutation responsible for late-onset cblC (MMACHC-R161Q), treatable with high dose OHCbl, is able to bind OHCbl with wild-type affinity, leaving undetermined the disease mechanism involved [Froese et al., Mechanism of responsiveness, Mol. Genet. Metab. (2009).]. To assess whether the mutation renders the protein unstable, we investigated the thermostability of the wild-type and mutant MMACHC proteins, either unbound or bound to different cobalamins (Cbl), using differential scanning fluorimetry. We found that MMACHC-wt and MMACHC-R161Q are both very thermolabile proteins in their apo forms, with melting temperatures (Tm) of 39.3±1.0 and 37.1±0.7°C, respectively; a difference confirmed by unfolding of MMACHC-R161Q but …
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