 |
PDBsum entry 1yfs
|
|
|
|
|
 |
Contents |
 |
|
|
|
|
|
|
|
|
|
|
|
|
* Residue conservation analysis
|
|
|
|
|
|
|
|
|
|
|
Enzyme class:
|
|
E.C.6.1.1.7
- alanine--tRNA ligase.
|
|
|
|
|
|
|
Reaction:
|
|
tRNA(Ala) + L-alanine + ATP = L-alanyl-tRNA(Ala) + AMP + diphosphate
|
|
|
|
|
|
tRNA(Ala)
|
+
|
L-alanine
Bound ligand (Het Group name = )
corresponds exactly
|
+
|
ATP
|
=
|
L-alanyl-tRNA(Ala)
|
+
|
AMP
|
+
|
diphosphate
|
|
|
|
|
|
|
|
|
|
|
|
|
Molecule diagrams generated from .mol files obtained from the
KEGG ftp site
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
| |
|
|
| |
|
DOI no:
|
Proc Natl Acad Sci U S A
102:988-993
(2005)
|
|
PubMed id:
|
|
|
|
|
|
| |
|
Breaking sieve for steric exclusion of a noncognate amino acid from active site of a tRNA synthetase.
|
|
M.A.Swairjo,
P.R.Schimmel.
|
|
|
|
|
| |
ABSTRACT
|
|
|
|
| |
|
|
The genetic code is fixed in aminoacylation reactions catalyzed by
aminoacyl-tRNA synthetases. Amino acid discrimination occurs at two sites: one
for amino acid activation and aminoacylation and one for editing misactivated
amino acids. Although the active site sieves out bulkier amino acids,
misactivation occurs with substrates whose side chains are smaller than the
cognate one. Paradoxically, although alanyl-tRNA synthetase activates glycine as
well as alanine, the sterically larger (than alanine) serine is also
misactivated. Here, we report crystal structures of an active fragment of
Aquifex aeolicus alanyl-tRNA synthetase complexed, separately, with Mg2+-ATP,
alanine, glycine, and serine. Ala and Gly are bound in similar orientations in a
side-chain-accommodating pocket, where alpha-amino and carboxyl groups are
stabilized by salt bridges, and the carboxyl by an H-bond from the side chain
NH2 of Asn-194. In contrast, whereas the same two salt bridges stabilize bound
Ser, H-bonding of the highly conserved (among class II tRNA synthetases) Asn-194
side chain NH2 to the Ser OH, instead of to the carboxyl, forces pocket
expansion. Significantly, in the Mg2+-ATP complex, Asn-194 coordinates a
Mg2+-alpha-phosphate bridge. Thus, the sieve for Ser exclusion is broken because
of selective pressure to retain Asn-194 for Mg2+-ATP and Ala binding.
|
|
|
|
|
|
| |
Selected figure(s)
|
|
|
|
| |
|
|
|
|
|
|
Figure 4.
Fig. 4. ATP binding by AlaRS. (A) Simulated annealed omit
F[o] - F[c] electron density map (resolution, 2.15 Å;
contour, 2.8  ) for the active site
region of AlaRS[453]/Mg2+-ATP complex, superimposed on the
refined model. The model for ATP, magnesium ions, and
surrounding atoms within a sphere of 3.2 Å was omitted
from map calculation. (B) Similar view showing active site
residues involved in ATP or magnesium binding. Model colors are
as in Fig. 1. Bound magnesium ions and water molecules are shown
as gray and red spheres, respectively. For clarity, some water
molecules and interactions with the ribose are not shown. (C)
Schematic of the interactions between enzyme, ATP, and
magnesium. Residues from motifs 2 and 3 are shown in orange and
cyan, respectively. Residues in black belong to strands in the
central  -sheet of the
active-site domain. Side chain conservation patterns among AlaRS
sequences from 80 organisms are shown in brackets (percentage
occurrence shown only for side chains present in >4% of the
sequences). Side chains without adjacent bracketed numbers are
invariant.
|
|
Figure 5.
Fig. 5. ATP-induced conformational changes in AlaRS[453]
active site. Cyan ribbon and side chains, apo AlaRS[453]; yellow
ribbon and colored side chains, complex with Mg2+-ATP.
|
|
|
|
| |
Figures were
selected
by an automated process.
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
 |
 |
|
Literature references that cite this PDB file's key reference
|
|
|
| |
PubMed id
|
|
Reference
|
|
|
|
|
|
M.Guo,
R.Shapiro,
P.Schimmel,
and
X.L.Yang
(2010).
Introduction of a leucine half-zipper engenders multiple high-quality crystals of a recalcitrant tRNA synthetase.
|
| |
Acta Crystallogr D Biol Crystallogr,
66,
243-250.
|
|
|
|
|
|
|
M.Guo,
Y.E.Chong,
R.Shapiro,
K.Beebe,
X.L.Yang,
and
P.Schimmel
(2009).
Paradox of mistranslation of serine for alanine caused by AlaRS recognition dilemma.
|
| |
Nature,
462,
808-812.
|
|
|
PDB codes:
|
|
|
|
|
|
|
|
M.Naganuma,
S.Sekine,
R.Fukunaga,
and
S.Yokoyama
(2009).
Unique protein architecture of alanyl-tRNA synthetase for aminoacylation, editing, and dimerization.
|
| |
Proc Natl Acad Sci U S A,
106,
8489-8494.
|
|
|
PDB codes:
|
|
|
|
|
|
|
|
M.Sokabe,
T.Ose,
A.Nakamura,
K.Tokunaga,
O.Nureki,
M.Yao,
and
I.Tanaka
(2009).
The structure of alanyl-tRNA synthetase with editing domain.
|
| |
Proc Natl Acad Sci U S A,
106,
11028-11033.
|
|
|
PDB codes:
|
|
|
|
|
|
|
|
R.A.Hellmann,
and
S.A.Martinis
(2009).
Defects in transient tRNA translocation bypass tRNA synthetase quality control mechanisms.
|
| |
J Biol Chem,
284,
11478-11484.
|
|
|
|
|
|
|
C.Liu,
H.Gamper,
S.Shtivelband,
S.Hauenstein,
J.J.Perona,
and
Y.M.Hou
(2007).
Kinetic quality control of anticodon recognition by a eukaryotic aminoacyl-tRNA synthetase.
|
| |
J Mol Biol,
367,
1063-1078.
|
|
|
|
|
|
|
R.Fukunaga,
and
S.Yokoyama
(2007).
Structure of the AlaX-M trans-editing enzyme from Pyrococcus horikoshii.
|
| |
Acta Crystallogr D Biol Crystallogr,
63,
390-400.
|
|
|
PDB code:
|
|
|
|
|
|
|
|
R.Fukunaga,
and
S.Yokoyama
(2007).
Crystallization and preliminary X-ray crystallographic study of alanyl-tRNA synthetase from the archaeon Archaeoglobus fulgidus.
|
| |
Acta Crystallogr Sect F Struct Biol Cryst Commun,
63,
224-228.
|
|
|
|
|
|
|
T.Crepin,
A.Yaremchuk,
M.Tukalo,
and
S.Cusack
(2006).
Structures of two bacterial prolyl-tRNA synthetases with and without a cis-editing domain.
|
| |
Structure,
14,
1511-1525.
|
|
|
PDB codes:
|
|
|
|
|
|
|
|
M.Sokabe,
A.Okada,
M.Yao,
T.Nakashima,
and
I.Tanaka
(2005).
Molecular basis of alanine discrimination in editing site.
|
| |
Proc Natl Acad Sci U S A,
102,
11669-11674.
|
|
|
PDB codes:
|
|
|
|
|
|
|
The most recent references are shown first.
Citation data come partly from CiteXplore and partly
from an automated harvesting procedure. Note that this is likely to be
only a partial list as not all journals are covered by
either method. However, we are continually building up the citation data
so more and more references will be included with time.
Where a reference describes a PDB structure, the PDB
codes are
shown on the right.
|
|
Links
