PDBsum entry 1q2u

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RNA binding protein PDB id
Protein chain
189 a.a. *
Waters ×195
* Residue conservation analysis

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Key reference
Title Crystal structure of dj-1/rs and implication on familial parkinson'S disease.
Authors Q.Huai, Y.Sun, H.Wang, L.S.Chin, L.Li, H.Robinson, H.Ke.
Ref. FEBS Lett, 2003, 549, 171-175. [DOI no: 10.1016/S0014-5793(03)00764-6]
PubMed id 12914946
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.
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.
Figure 2.
Fig. 2. Superposition of DJ-1 (golden) over intracellular protease PH1704 (cyan, left) and E. coli heat shock protein HSP31 (green, right).
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.
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.
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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