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| Content Provider | Journal of Biological Chemistry (JBC) |
|---|---|
| Author | Kumasaka, Takashi Aritake, Kosuke Ago, Hideo Irikura, Daisuke Tsurumura, Toshiharu Yamamoto, Masaki Miyano, Masashi Urade, Yoshihiro Hayaishi, Osamu |
| Abstract | Lipocalin type prostaglandin D synthase (L-PGDS) is a multifunctional protein acting as a somnogen (PGD2)-producing enzyme, an extracellular transporter of various lipophilic ligands, and an amyloid-β chaperone in human cerebrospinal fluid. In this study, we determined the crystal structures of two different conformers of mouse L-PGDS, one with an open cavity of the β-barrel and the other with a closed cavity due to the movement of the flexible E-F loop. The upper compartment of the central large cavity contains the catalytically essential Cys65 residue and its network of hydrogen bonds with the polar residues Ser45, Thr67, and Ser81, whereas the lower compartment is composed of hydrophobic amino acid residues that are highly conserved among other lipocalins. SH titration analysis combined with site-directed mutagenesis revealed that the Cys65 residue is activated by its interaction with Ser45 and Thr67 and that the S45A/T67A/S81A mutant showed less than 10% of the L-PGDS activity. The conformational change between the open and closed states of the cavity indicates that the mobile calyx contributes to the multiligand binding ability of L-PGDS. |
| Related Links | http://www.jbc.org/content/284/33/22344.abstract |
| Ending Page | 22352 |
| Starting Page | 22344 |
| Page Count | 9 |
| File Format | HTM / HTML PDF |
| ISSN | 00219258 |
| Journal | Journal of Biological Chemistry (JBC) |
| Issue Number | 33 |
| Volume Number | 284 |
| DOI | 10.1074/jbc.M109.018341 |
| e-ISSN | 1083351X |
| Language | English |
| Publisher | American Society for Biochemistry and Molecular Biology |
| Publisher Date | 2009-08-14 |
| Access Restriction | Open |
| Subject Keyword | Lipids and Lipoproteins: Metabolism, Regulation, and Signaling |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Biochemistry Molecular Biology |
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