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Sense/Antisense origins of amino acid activation
Author(s) -
Carter Charles Williams,
Pham Yen,
Li Li,
Weinreb Violetta
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a504
Subject(s) - amino acid , peptide , alanine , transfer rna , gene , chemistry , biology , stereochemistry , biochemistry , rna
Sequence and structure alignments of class I aminoacyl‐tRNA synthetases (aaRS) reveal that a minimal catalytic domain of ~130 amino acids can be achieved by removing 76 residues from the catalytic domain of TrpRS and connecting the resulting termini by a peptide bond. The deleted peptide, known as CP1, provides interfaces to the anticodon‐binding domains, to the second monomers in dimeric class Ic aaRS, and editing and 3′ acceptor‐binding domains in different class I subclasses. The minimal TrpRS catalytic core domain constructed by deleting CP1, together with the C‐terminal anticodon‐binding domain, retains all catalytic signature peptides and all residues defining amino acid specificity. It catalyzes tryptophan activation approximately 10 11 times faster than the uncatalyzed rate, and an active site point mutant changes its activity. This high residual activity demonstrates that ancestral class I aaRS could have been as small as ~130 residues and that codons for Class I PxxxHIGH and KMSKS signatures could have been aligned in‐frame and antisense to those for the Motif 2 and Motif 1 sequences of ancestral class II aaRS genes, as proposed by Rodin and Ohno (1995. Orig. Life Evol. Biosph. 25, 565–589). Thus, class I and II synthetases could have arisen on a sense/antisense double open reading frame in the same gene, as is observed for their homologs, HSP70 and glutamate dehydrogenase, in a contemporary fungus (LéJohn, H. B., et al., (1994), JBC 269 , –4531; Carter, C. W., Jr. & Duax, W. L. (2002). Mol. Cell 10 , –708). Supported by NIGMS.