| Literature References | 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,
PP.126-128.
2. DELARUE, M.
Aminoacyl-tRNA synthetases.
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
Glutaminyl-tRNA Synthetase.
BIOCHEMISTRY 32 8758-8771 (1993).
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| Documentation | 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
[1].
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 [3], 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 6.1.1.16) 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.
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