lipocalin-type prostaglandin D synthaselipocalin-type prostaglandin D synthase
Structural highlights
2czt is a 1 chain structure with sequence from Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
PTGDS_MOUSE Catalyzes the conversion of PGH2 to PGD2, a prostaglandin involved in smooth muscle contraction/relaxation and a potent inhibitor of platelet aggregation. Involved in a variety of CNS functions, such as sedation, NREM sleep and PGE2-induced allodynia, and may have an anti-apoptotic role in oligodendrocytes. Binds small non-substrate lipophilic molecules, including biliverdin, bilirubin, retinal, retinoic acid and thyroid hormone, and may act as a scavenger for harmful hydrophopic molecules and as a secretory retinoid and thyroid hormone transporter. Possibly involved in development and maintenance of the blood-brain, blood-retina, blood-aqueous humor and blood-testis barrier. It is likely to play important roles in both maturation and maintenance of the central nervous system and male reproductive system.[1][2][3][4][5][6][7][8]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
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-beta 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 beta-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.
Structural basis of the catalytic mechanism operating in open-closed conformers of lipocalin type prostaglandin D synthase.,Kumasaka T, Aritake K, Ago H, Irikura D, Tsurumura T, Yamamoto M, Miyano M, Urade Y, Hayaishi O J Biol Chem. 2009 Aug 14;284(33):22344-52. Epub 2009 Jun 22. PMID:19546224[9]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
↑Eguchi N, Minami T, Shirafuji N, Kanaoka Y, Tanaka T, Nagata A, Yoshida N, Urade Y, Ito S, Hayaishi O. Lack of tactile pain (allodynia) in lipocalin-type prostaglandin D synthase-deficient mice. Proc Natl Acad Sci U S A. 1999 Jan 19;96(2):726-30. PMID:9892701
↑Pinzar E, Kanaoka Y, Inui T, Eguchi N, Urade Y, Hayaishi O. Prostaglandin D synthase gene is involved in the regulation of non-rapid eye movement sleep. Proc Natl Acad Sci U S A. 2000 Apr 25;97(9):4903-7. PMID:10781097 doi:http://dx.doi.org/10.1073/pnas.090093997
↑Fujitani Y, Kanaoka Y, Aritake K, Uodome N, Okazaki-Hatake K, Urade Y. Pronounced eosinophilic lung inflammation and Th2 cytokine release in human lipocalin-type prostaglandin D synthase transgenic mice. J Immunol. 2002 Jan 1;168(1):443-9. PMID:11751991
↑Taniike M, Mohri I, Eguchi N, Beuckmann CT, Suzuki K, Urade Y. Perineuronal oligodendrocytes protect against neuronal apoptosis through the production of lipocalin-type prostaglandin D synthase in a genetic demyelinating model. J Neurosci. 2002 Jun 15;22(12):4885-96. PMID:12077186
↑Shimamoto S, Yoshida T, Inui T, Gohda K, Kobayashi Y, Fujimori K, Tsurumura T, Aritake K, Urade Y, Ohkubo T. NMR solution structure of lipocalin-type prostaglandin D synthase: evidence for partial overlapping of catalytic pocket and retinoic acid-binding pocket within the central cavity. J Biol Chem. 2007 Oct 26;282(43):31373-9. Epub 2007 Aug 22. PMID:17715133 doi:10.1074/jbc.M700123200
↑Kumasaka T, Aritake K, Ago H, Irikura D, Tsurumura T, Yamamoto M, Miyano M, Urade Y, Hayaishi O. Structural basis of the catalytic mechanism operating in open-closed conformers of lipocalin type prostaglandin D synthase. J Biol Chem. 2009 Aug 14;284(33):22344-52. Epub 2009 Jun 22. PMID:19546224 doi:10.1074/jbc.M109.018341
↑Miyamoto Y, Nishimura S, Inoue K, Shimamoto S, Yoshida T, Fukuhara A, Yamada M, Urade Y, Yagi N, Ohkubo T, Inui T. Structural analysis of lipocalin-type prostaglandin D synthase complexed with biliverdin by small-angle X-ray scattering and multi-dimensional NMR. J Struct Biol. 2010 Feb;169(2):209-18. Epub 2009 Oct 13. PMID:19833210 doi:10.1016/j.jsb.2009.10.005
↑Kumasaka T, Aritake K, Ago H, Irikura D, Tsurumura T, Yamamoto M, Miyano M, Urade Y, Hayaishi O. Structural basis of the catalytic mechanism operating in open-closed conformers of lipocalin type prostaglandin D synthase. J Biol Chem. 2009 Aug 14;284(33):22344-52. Epub 2009 Jun 22. PMID:19546224 doi:10.1074/jbc.M109.018341
