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PDBsum entry 2q5h
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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 structure of apo-wildtype glycyl-tRNA synthetase
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Structure:
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Glycyl-tRNA synthetase. Chain: a. Fragment: residues 55-739. Synonym: glycine-tRNA ligase, glyrs. Engineered: yes
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Gene: gars. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
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Resolution:
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3.00Å
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R-factor:
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0.207
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R-free:
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0.250
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Authors:
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M.Z.Cader,J.Ren,P.A.James,L.E.Bird,K.Talbot,D.K.Stammers,Oxford Protein Production Facility (Oppf)
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Key ref:
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M.Z.Cader
et al.
(2007).
Crystal structure of human wildtype and S581L-mutant glycyl-tRNA synthetase, an enzyme underlying distal spinal muscular atrophy.
Febs Lett,
581,
2959-2964.
PubMed id:
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Date:
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01-Jun-07
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Release date:
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19-Jun-07
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PROCHECK
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Headers
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References
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P41250
(GARS_HUMAN) -
Glycine--tRNA ligase from Homo sapiens
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Seq:
Struc:
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739 a.a.
528 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 2:
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E.C.2.7.7.-
- ?????
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Enzyme class 3:
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E.C.6.1.1.14
- glycine--tRNA ligase.
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Reaction:
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tRNA(Gly) + glycine + ATP = glycyl-tRNA(Gly) + AMP + diphosphate
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tRNA(Gly)
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+
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glycine
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+
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ATP
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=
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glycyl-tRNA(Gly)
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+
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AMP
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+
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diphosphate
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Note, where more than one E.C. class is given (as above), each may
correspond to a different protein domain or, in the case of polyprotein
precursors, to a different mature protein.
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Molecule diagrams generated from .mol files obtained from the
KEGG ftp site
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Febs Lett
581:2959-2964
(2007)
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PubMed id:
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Crystal structure of human wildtype and S581L-mutant glycyl-tRNA synthetase, an enzyme underlying distal spinal muscular atrophy.
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M.Z.Cader,
J.Ren,
P.A.James,
L.E.Bird,
K.Talbot,
D.K.Stammers.
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ABSTRACT
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Dominant mutations in the ubiquitous enzyme glycyl-tRNA synthetase (GlyRS),
including S581L, lead to motor nerve degeneration. We have determined crystal
structures of wildtype and S581L-mutant human GlyRS. The S581L mutation is
approximately 50A from the active site, and yet gives reduced aminoacylation
activity. The overall structures of wildtype and S581L-GlyRS, including the
active site, are very similar. However, residues 567-575 of the
anticodon-binding domain shift position and in turn could indirectly affect
glycine binding via the tRNA or alternatively inhibit conformational changes.
Reduced enzyme activity may underlie neuronal degeneration, although a
dominant-negative effect is more likely in this autosomal dominant disorder.
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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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W.W.Motley,
K.Talbot,
and
K.H.Fischbeck
(2010).
GARS axonopathy: not every neuron's cup of tRNA.
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Trends Neurosci,
33,
59-66.
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F.Achilli,
V.Bros-Facer,
H.P.Williams,
G.T.Banks,
M.AlQatari,
R.Chia,
V.Tucci,
M.Groves,
C.D.Nickols,
K.L.Seburn,
R.Kendall,
M.Z.Cader,
K.Talbot,
J.van Minnen,
R.W.Burgess,
S.Brandner,
J.E.Martin,
M.Koltzenburg,
L.Greensmith,
P.M.Nolan,
and
E.M.Fisher
(2009).
An ENU-induced mutation in mouse glycyl-tRNA synthetase (GARS) causes peripheral sensory and motor phenotypes creating a model of Charcot-Marie-Tooth type 2D peripheral neuropathy.
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Dis Model Mech,
2,
359-373.
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R.T.Guo,
Y.E.Chong,
M.Guo,
and
X.L.Yang
(2009).
Crystal structures and biochemical analyses suggest a unique mechanism and role for human glycyl-tRNA synthetase in Ap4A homeostasis.
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J Biol Chem,
284,
28968-28976.
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A.Antonellis,
and
E.D.Green
(2008).
The role of aminoacyl-tRNA synthetases in genetic diseases.
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Annu Rev Genomics Hum Genet,
9,
87.
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S.G.Park,
P.Schimmel,
and
S.Kim
(2008).
Aminoacyl tRNA synthetases and their connections to disease.
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Proc Natl Acad Sci U S A,
105,
11043-11049.
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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.
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Links
