Literature summary for 6.1.1.7 extracted from

Sun, L.; Song, Y.; Blocquel, D.; Yang, X.L.; Schimmel, P.
Two crystal structures reveal design for repurposing the C-Ala domain of human AlaRS (2016), Proc. Natl. Acad. Sci. USA, 113, 14300-14305 .

Cloned(Commentary)

Cloned (Comment)	Organism
gene alaS, sequence comparisons, recombinant expression of a C-Ala construct consisting of the C-terminal 757-968 amino acids	Homo sapiens

Crystallization (Commentary)

Crystallization (Comment)	Organism
purified recombinant appended C-terminal domain (C-Ala), two different crystal forms, each of which is specific to a particular condition are achieved, one of these crystal forms harbors the monomer and is obtained using 0.1 M Tris, pH 8.5, and 25% w/v PEG 3350, whereas the other captures a dimer using 0.2 M ammonium acetate, 0.1 M Tris, pH 8.5, and 25% w/v PEG 3350, X-ray diffraction structure determination and analysis	Homo sapiens

Crystallization (Comment)

Organism

purified recombinant appended C-terminal domain (C-Ala), two different crystal forms, each of which is specific to a particular condition are achieved, one of these crystal forms harbors the monomer and is obtained using 0.1 M Tris, pH 8.5, and 25% w/v PEG 3350, whereas the other captures a dimer using 0.2 M ammonium acetate, 0.1 M Tris, pH 8.5, and 25% w/v PEG 3350, X-ray diffraction structure determination and analysis

Homo sapiens

Protein Variants

Protein Variants	Comment	Organism
additional information	construction of an isolated appended C-terminal domain (C-Ala) consisting of the C-terminal 757968 amino acids, the 23 kDa protein forms dimers as well as monomers, and locates in the nucleus	Homo sapiens

Localization

Localization	Comment	Organism	GeneOntology No.	Textmining
additional information	an isolated 23 kDa appended C-terminal domain (C-Ala), consisting of the C-terminal 757968 amino acids, locates in the nucleus	Homo sapiens	-	-

Organism

Organism	UniProt	Comment	Textmining
Homo sapiens	Q5JTZ9	-	-

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.	Reac.
additional information	recombinant mutant human appended C-terminal domain (C-Ala) shows strong binding to DNA cellulose, but not to cellulose alone	Homo sapiens	?	-	?

Subunits

Subunits	Comment	Organism
dimer	wild-type enzyme, gel filtration and sequence calculation	Homo sapiens
More	an isolated appended C-terminal domain (C-Ala), consisting of the C-terminal 757968 amino acids, forms dimers as well as monomers, gel filtration	Homo sapiens

Synonyms

Synonyms	Comment	Organism
Alanyl-tRNA synthetase	-	Homo sapiens
AlaRS	-	Homo sapiens

General Information

General Information	Comment	Organism
evolution	the sequence of appended C-terminal domain (C-Ala) of enzyme AlaRS diverged widely in the evolutionary progression to humans. During evolution, 19 aaRSs expanded by acquiring novel noncatalytic appended domains, which are absent from bacteria and many lower eukaryotes but confer extracellular and nuclear functions in higher organisms. AlaRS is the single exception, with an appended C-terminal domain (C-Ala) that is conserved from prokaryotes to humans but with a wide sequence divergence. In human cells, C-Ala is also a splice variant of AlaRS. Crystal structures of two forms of human C-Ala, and small-angle X-ray scattering of AlaRS, show that the large sequence divergence of human C-Ala reshaped C-Ala in a way that changed the global architecture of AlaRS. This reshaping removed the role of C-Ala in prokaryotes for docking tRNA and instead repurposed it to form a dimer interface presenting a DNA-binding groove. This groove cannot form with the bacterial ortholog. Direct DNA binding by human C-Ala, but not by bacterial C-Ala. Instead of acquiring a special appended domain, a new AlaRS architecture has benn created by diversifying a preexisting domain	Homo sapiens