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* Residue conservation analysis
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PDB id:
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Ligase
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Title:
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Crystal structures of human tryptophanyl-tRNA synthetase in with trpamp
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Structure:
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Tryptophanyl-tRNA synthetase. Chain: a, b. Synonym: tryptophan-tRNA ligase, trprs, interferon-induced 53, ifp53, hwrs. Engineered: yes
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Gene: wars, ifi53, wrs. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
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Resolution:
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2.42Å
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R-factor:
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0.214
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R-free:
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0.238
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Authors:
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N.Shen,J.P.Ding
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Key ref:
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N.Shen
et al.
(2008).
Catalytic mechanism of the tryptophan activation reaction revealed by crystal structures of human tryptophanyl-tRNA synthetase in different enzymatic states.
Nucleic Acids Res,
36,
1288-1299.
PubMed id:
DOI:
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Date:
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05-Aug-07
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Release date:
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29-Apr-08
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PROCHECK
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Headers
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References
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P23381
(SYWC_HUMAN) -
Tryptophanyl-tRNA synthetase, cytoplasmic
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Seq:
Struc:
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471 a.a.
388 a.a.
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Key: |
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PfamA domain |
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Secondary structure |
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CATH domain |
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Enzyme class:
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E.C.6.1.1.2
- Tryptophan--tRNA ligase.
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Reaction:
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ATP + L-tryptophan + tRNA(Trp) = AMP + diphosphate + L-tryptophyl- tRNA(Trp)
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ATP
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+
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L-tryptophan
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+
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tRNA(Trp)
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=
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AMP
Bound ligand (Het Group name = )
matches with 62.16% similarity
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diphosphate
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L-tryptophyl- tRNA(Trp)
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Molecule diagrams generated from .mol files obtained from the
KEGG ftp site
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Gene Ontology (GO) functional annotation
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Cellular component
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soluble fraction
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3 terms
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Biological process
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gene expression
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7 terms
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Biochemical function
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nucleotide binding
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6 terms
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DOI no:
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Nucleic Acids Res
36:1288-1299
(2008)
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PubMed id:
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Catalytic mechanism of the tryptophan activation reaction revealed by crystal structures of human tryptophanyl-tRNA synthetase in different enzymatic states.
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N.Shen,
M.Zhou,
B.Yang,
Y.Yu,
X.Dong,
J.Ding.
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ABSTRACT
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Human tryptophanyl-tRNA synthetase (hTrpRS) differs from its bacterial
counterpart at several key positions of the catalytic active site and has an
extra N-terminal domain, implying possibly a different catalytic mechanism. We
report here the crystal structures of hTrpRS in complexes with Trp,
tryptophanamide and ATP and tryptophanyl-AMP, respectively, which represent
three different enzymatic states of the Trp activation reaction. Analyses of
these structures reveal the molecular basis of the mechanisms of the substrate
recognition and the activation reaction. The dimeric hTrpRS is structurally and
functionally asymmetric with half-of-the-sites reactivity. Recognition of Trp is
by an induced-fit mechanism involving conformational change of the AIDQ motif
that creates a perfect pocket for the binding and activation of Trp and causes
coupled movements of the N-terminal and C-terminal domains. The KMSAS loop
appears to have an inherent flexibility and the binding of ATP stabilizes it in
a closed conformation that secures the position of ATP for catalysis. Our
structural data indicate that the catalytic mechanism of the Trp activation
reaction by hTrpRS involves more moderate conformational changes of the
structural elements at the active site to recognize and bind the substrates,
which is more complex and fine-tuned than that of bacterial TrpRS.
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Literature references that cite this PDB file's key reference
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PubMed id
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Reference
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M.Zhou,
X.Dong,
N.Shen,
C.Zhong,
and
J.Ding
(2010).
Crystal structures of Saccharomyces cerevisiae tryptophanyl-tRNA synthetase: new insights into the mechanism of tryptophan activation and implications for anti-fungal drug design.
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Nucleic Acids Res, 38,
3399-3413.
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PDB codes:
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X.Dong,
M.Zhou,
C.Zhong,
B.Yang,
N.Shen,
and
J.Ding
(2010).
Crystal structure of Pyrococcus horikoshii tryptophanyl-tRNA synthetase and structure-based phylogenetic analysis suggest an archaeal origin of tryptophanyl-tRNA synthetase.
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Nucleic Acids Res, 38,
1401-1412.
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I.A.Vasil'eva,
E.A.Semenova,
and
N.A.Moor
(2009).
Interaction of human phenylalanyl-tRNA synthetase with specific tRNA according to thiophosphate footprinting.
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Biochemistry (Mosc), 74,
175-185.
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J.Lee,
J.Johnson,
Z.Ding,
M.Paetzel,
and
R.B.Cornell
(2009).
Crystal structure of a mammalian CTP: phosphocholine cytidylyltransferase catalytic domain reveals novel active site residues within a highly conserved nucleotidyltransferase fold.
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J Biol Chem, 284,
33535-33548.
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PDB code:
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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.
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Links
