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PDBsum entry 1q2u
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RNA binding protein
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PDB id
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1q2u
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Contents |
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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Crystal structure of dj-1/rs and implication on familial parkinson'S disease.
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Authors
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Q.Huai,
Y.Sun,
H.Wang,
L.S.Chin,
L.Li,
H.Robinson,
H.Ke.
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Ref.
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FEBS Lett, 2003,
549,
171-175.
[DOI no: ]
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PubMed id
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Abstract
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DJ-1 is a protein involved in multiple physiological processes, including
cancer, Parkinson's disease, and male fertility. It is unknown how DJ-1
functions in the apparently different systems. The crystal structure of DJ-1 at
1.6 A resolution shows that DJ-1 is a helix-strand-helix sandwich and forms a
dimer. The DJ-1 structure is similar to the members of the intracellular
protease PfpI family. However, the catalytic triad of Cys-His-Glu is not
strictly conserved in DJ-1, implying that DJ-1 has a different catalytic
mechanism if it acts as a protease or DJ-1 serves as a regulatory protein in the
physiological processes. The structure shows that Leu166 positions in the middle
of a helix and thus predicts that the L166P mutation will bend the helix and
impact the dimerization of DJ-1. As a result, the conformational changes may
diminish the DJ-1 binding with its partner, leading to the familial Parkinson's
disease caused by the single L166P mutation.
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Figure 1.
Fig. 1. Ribbon representation of monomeric DJ-1 in two
different views (a and b), and DJ-1 dimer (c and d). The red
balls in c and d represent Leu166 that is located in the middle
of helix H7. The purple balls are Lys130, (e) the secondary
structure and sequence.
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Figure 2.
Fig. 2. Superposition of DJ-1 (golden) over intracellular
protease PH1704 (cyan, left) and E. coli heat shock protein
HSP31 (green, right).
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Figure 3.
Fig. 3. The catalytic triad of Cys100–His101 and Glu74 at
the active site of PH1704 (left). The dotted lines represent the
hydrogen bonds. Residue Glu74 comes from the neighboring subunit
in the hexamer of PH1704. Right, a putative binding pocket of
DJ-1. The catalytic triad is not conserved in DJ-1, but the
pocket may still be capable of binding with its substrate
proteins.
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Figure 4.
Fig. 4. The interfacial region of DJ-1 dimer and the
position of Leu166. Two helices H7 and H8 are shown in the
similar orientation as in Fig. 1d. The L166P mutation is
expected to cause significant conformational changes and to
impact the dimerization of DJ-1.
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The above figures are
reprinted
by permission from the Federation of European Biochemical Societies:
FEBS Lett
(2003,
549,
171-175)
copyright 2003.
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