Discovered in 2003, this is the first example of an aminoacyl tRNA synthetase
being implicated in any inherited human disorder, and so far 11 pathogenic missense GARS variants have been linked to not only dSMA-V but also Charcot-Marie-Tooth disease type 2D (CMT2D) .
However, Schimmel and his colleagues have now (http://www.pnas.org/content/early/2016/11/23/1617316113) discovered an aminoacyl tRNA synthetase
called AlaRS that lacks any new decorations and can somehow still carry out its new role in humans without overhauling its basic architecture.
Physiocrines are derived from aminoacyl tRNA synthetases
, which have been known for decades to function intracellularly in protein synthesis.
The top-half domain, sometimes referred to as a tRNA "minihelix," has been shown to provide the determinants necessary for specific charging by aminoacyl tRNA synthetases
(14, 15); for interaction with elongation factor Tu (16); for 5[prime] processing by RNase P (17); and for distinguishing elongator from initiator tRNA (18).