1. LODISH, H., BALTIMORE, D., BERK, A., ZIPURSKY, S.L., MATSUDAIRA, P.
AND DARNELL, J.
Nucleic Acids, the Genetic Code, and Protein Synthesis.
IN MOLECULAR CELL BIOLOGY, SCIENTIFIC AMERICAN BOOKS (NEW YORK), 1995,
2. DELARUE, M.
CURR.OPIN.STRUCT.BIOL. 5 48-55 (1995).
3. PERONA, J.J., ROULD, M. AND STEITZ, T.A.
Structural Basis for Transfer RNA Aminoacylation by Escherichia coli
BIOCHEMISTRY 32 8758-8771 (1993).
Appropriate attachment of an amino acid to its cognate tRNA is the key to
faithful translation of the genetic code. The family of enzymes responsible
for this is the aminoacyl-tRNA synthetases (AATRSs) (EC 6.1.1.-).
AATRSs catalyse a two-step reaction:
(1) Enzyme + amino acid + ATP ---> Enzyme(aminoacyl-AMP) + PPi
(2) tRNA + Enzyme(aminoacyl-AMP) ---> aminoacyl-tRNA + AMP + Enzyme
In the first step, they form an aminoacyl-adenylate, in which the carboxyl
of the amino acid is linked to the alpha-phosphate of ATP, by displacing
the pyrophosphate. When the correct tRNA is bound, the aminoacyl group is
transferred to the 2'- or 3'-terminal OH of the tRNA at the expense of AMP
Based on structural and sequence comparisons, this group of at least 20
proteins (in prokaryotes there are approximately 20, but in eukaryotes
there are usually 2 forms for each amino acid; namely, the cytosolic and
mitochondrial forms) can be divided into two classes.
Class I AATRSs contain a characteristic Rossman fold and are mostly
monomeric. At the primary structure level, two highly-conserved motifs are
observed, `HIGH' and `KMSKS' [2,3]; these are associated with the ATP-
binding site in these synthetases.
Class II AATRSs share an anti-parallel beta-sheet formation, flanked by
alpha-helices , and are mostly dimeric or multimeric.
Further distinction between the two classes is evident when the reaction
mechanisms are investigated. In reactions catalysed by the class I AATRSs,
the aminoacyl group is coupled to the 2'-hydroxyl of the tRNA, while, in
class II reactions, the 3'-hydroxyl site is preferred.
Cysteinyl-tRNA synthetase (EC 188.8.131.52) is specific to cysteine and belongs
to class I.
TRNASYNTHCYS is a 4-element fingerprint that provides a signature for
cysteinyl-tRNA synthetases. The fingerprint was derived from an initial
alignment of 7 sequences: the motifs were drawn from the N-terminal and
central regions of the alignment - motif 1 lies adjacent to the `HIGH'
region; and motif 5 lies next to the `KMSKS' region. Two iterations on
OWL30.2 were required to reach convergence, at which point a true set
comprising 16 sequences was identified. Several partial matches were also
found: with the exception of MTCY26124 and MTCY27037, which are cosmids
containing partial cds, all are AATRS fragments.
An update on SPTR37_9f identified a true set of 22 sequences.